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1.
Exp Eye Res ; 238: 109743, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38056550

RESUMEN

Pigment epithelium-derived factor (PEDF) is widely recognized as a neuroprotective factor expressed in the retina and has shown therapeutic potential in several retinal diseases. Our study aimed to identify the neuroprotective fragment in PEDF and investigate its protective activity in retinas under ischemia-reperfusion (IR) condition. We synthesized a series of shorter synthetic peptides, 6-mer (Ser93-Gln98) and its d-form variant (6 dS) derived from the 44-mer (Val78-Thr121; a PEDF neurotrophic fragment), to determine their cytoprotective activity in IR injury, which was induced in rat retinas by injection of saline into the anterior chamber to increase the intraocular pressure (IOP) followed by reperfusion. We found the cytoprotective effect of 6-mer on glutamate-treated Neuro-2a cells and tert-butyl hydroperoxide (tBHP)-treated 661W cells were 2.6-fold and 1.5-fold higher than the 44-mer, respectively. The cytoprotective effect was blocked by a chemical inhibitor atglistatin and blocking antibody targeting PEDF receptor (PEDF-R). IR induced several impairments in retina, including cell apoptosis, activation of microglia/macroglia, degeneration of retinal capillaries, reduction in electroretinography (ERG) amplitudes, and retinal atrophy. Such IR injuries were ameliorated by treatment with 6-mer and 6 dS eye drops. Also, the neuroprotective activity of 6-mer and 6 dS in ischemic retinas were dramatically reversed by atglistatin preconditioning. Taken together, our data demonstrate smallest neuroprotective fragment of PEDF has potential to treat retinal degeneration-related diseases.


Asunto(s)
Proteínas del Ojo , Factores de Crecimiento Nervioso , Daño por Reperfusión , Retina , Retinitis , Serpinas , Animales , Ratas , Conejos , Factores de Crecimiento Nervioso/administración & dosificación , Factores de Crecimiento Nervioso/química , Factores de Crecimiento Nervioso/metabolismo , Proteínas del Ojo/administración & dosificación , Proteínas del Ojo/química , Proteínas del Ojo/metabolismo , Serpinas/administración & dosificación , Serpinas/química , Serpinas/metabolismo , Retina/metabolismo , Retina/patología , Daño por Reperfusión/metabolismo , Citoprotección , Apoptosis , Neuronas/metabolismo , Retinitis/tratamiento farmacológico , Retinitis/metabolismo , Administración Tópica , Péptidos/administración & dosificación , Péptidos/metabolismo
2.
Inorg Chem ; 63(15): 6714-6722, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38557020

RESUMEN

Converting CO2 into valuable chemicals via sustainable energy sources is indispensable for human development. Photothermal catalysis combines the high selectivity of photocatalysis and the high yield of thermal catalysis, which is promising for CO2 reduction. However, the present photothermal catalysts suffer from low activity due to their poor light absorption ability and fast recombination of photogenerated electrons and holes. Here, a TiO2@Bi2WO6 heterojunction photocatalyst featuring a hierarchical hollow structure was prepared by an in situ growth method. The visible light absorption and photothermal effect of the TiO2@Bi2WO6 photocatalyst is promoted by a hierarchical hollow structure, while the recombination phenomenon is significantly mitigated due to the construction of the heterojunction interface and the existence of excited Bi(3-x)+ sites. Such a catalyst exhibits excellent photothermal performance with a CO yield of 43.7 µmol h-1 g-1, which is 15 and 4.7 times higher than that of pure Bi2WO6 and that of physically mixed TiO2/Bi2WO6, respectively. An in situ study shows that the pathway for the transformation of CO2 into CO over our TiO2@Bi2WO6 proceeds via two important intermediates, including COO- and COOH-. Our work provides a new idea of excited states for the design and synthesis of highly efficient photothermal catalysts for CO2 conversion.

3.
Ecotoxicol Environ Saf ; 284: 116894, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39154500

RESUMEN

BACKGROUND: Ambient air pollution might serve as a prognostic factor for ovarian cancer (OC) survival, yet the relationships between plant-based diet indices (PDIs) and OC survival remain unclear. We aimed to investigate the associations of comprehensive air pollution and PDIs with OC survival and explored the effects of air pollution-diet interactions. METHODS: The present study encompassed 658 patients diagnosed with OC. The overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI (uPDI) were evaluated by a self-reported validated food frequency questionnaire. In addition, an air pollution score (APS) was formulated by summing the concentrations of particulate matter with a diameter of 2.5 microns or less, ozone, and nitrogen dioxide. Cox proportional hazard models were applied to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs). The potential interactions of APS with PDIs in relation to overall survival (OS) were assessed on both multiplicative and additive scales. RESULTS: Throughout a median follow-up of 37.60 (interquartile: 24.77-50.70) months, 123 deaths were confirmed. Comparing to the lowest tertiles, highest uPDI was associated with lower OS of OC (HR = 2.06, 95 % CI = 1.30, 3.28; P-trend < 0.01), whereas no significant associations were found between either overall PDI or hPDI and OC survival. Higher APS (HR for per interquartile range = 1.27, 95 % CI = 1.01, 1.60) was significantly associated with worse OC survival, and the association was exacerbated by adherence to uPDI. Notably, an additive interaction was identified between combined air pollution and uPDI (P < 0.005 for high APS and high uPDI). We also found that adherence to overall PDI aggravated associations of air pollution with OC survival (P-interaction = 0.006). CONCLUSIONS: Joint exposure to various ambient air pollutants was significantly associated with lower survival among patients with OC, particularly for those who predominantly consumed unhealthy plant-based foods.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Neoplasias Ováricas , Material Particulado , Femenino , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias Ováricas/mortalidad , Contaminación del Aire/efectos adversos , Contaminación del Aire/estadística & datos numéricos , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/efectos adversos , Adulto , Dieta Vegetariana , Modelos de Riesgos Proporcionales , Ozono/análisis , Anciano , Dióxido de Nitrógeno/análisis , Exposición a Riesgos Ambientales/estadística & datos numéricos , Exposición a Riesgos Ambientales/efectos adversos , Estudios de Cohortes , Dieta a Base de Plantas
4.
J Asian Nat Prod Res ; 26(3): 293-301, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37162445

RESUMEN

Four new iridoid glycosides (1-4), rehmaglutosides L-O, were isolated from the air-dried roots of Rehmannia glutinosa. Their structures were established from the spectroscopic data obtained and by chemical evidence. The known mellittoside (5) and ajugol (6) were also obtained in the current investigation, and the structure of mellittoside was unequivocally defined using X-ray diffraction data. Compounds 1-6 were tested for their cytotoxicity against five human tumor cell lines and proliferation effects on Lactobacillus Reuteri.


Asunto(s)
Glicósidos , Rehmannia , Humanos , Glicósidos/farmacología , Glicósidos/química , Rehmannia/química , Glicósidos Iridoides/farmacología
5.
J Asian Nat Prod Res ; 26(2): 280-292, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36877100

RESUMEN

Seven new pentasaccharides (1-7), rehmaglupentasaccharides A-G, were isolated from the air-dried roots of Rehmannia glutinosa. Their structures were established from the spectroscopic data obtained and by chemical evidence. The known verbascose (8) and stachyose (9) were also obtained in the current investigation, and the structure of stachyose was unequivocally defined using X-ray diffraction data. Compounds 1-9 were tested for their cytotoxicity against five human tumor cell lines, influence on dopamine receptor activation, and proliferation effects against Lactobacillus reuteri.


Asunto(s)
Rehmannia , Humanos , Rehmannia/química , Línea Celular , Raíces de Plantas/química
6.
J Asian Nat Prod Res ; : 1-9, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39329329

RESUMEN

Three new cyclopentanoid monoterpenes, neopiscrocins A-C (1-3), together with 14 known compounds (4-17), were isolated from the roots of Picrorhiza scrophulariiflora. The structres of these compounds were elucidated on the basis of their spectroscopic data. All compounds were evaluated for cytotoxicity against six human tumor cell lines (PC9, PANC1, HCT-116, Hep-G2, BGC-823, and MCF-7), hepatoprotective activity and anti-inflammatory activity.

7.
Phytother Res ; 37(6): 2262-2279, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36726293

RESUMEN

Distal metastases from breast cancer, especially bone metastases, are extremely common in the late stages of the disease and are associated with a poor prognosis. EMT is a biomarker of the early process of bone metastasis, and MMP-9 and MMP-13 are important osteoclastic activators. Previously, we found that meso-Hannokinol (HA) could significantly inhibit EMT and MMP-9 and MMP-13 expressions in breast cancer cells. On this basis, we further explored the role of HA in breast cancer bone metastasis. In vivo, we established a breast cancer bone metastasis model by intracardially injecting breast cancer cells. Intraperitoneal injections of HA significantly reduced breast cancer cell metastasis to the leg bone in mice and osteolytic lesions caused by breast cancer. In vitro, HA inhibited the migration and invasion of breast cancer cells and suppressed the expressions of EMT, MMP-9, MMP-13, and other osteoclastic activators. HA inhibited EMT and MMP-9 by activating the ROS/JNK pathway as demonstrated by siJNK and SP600125 inhibition of JNK phosphorylation and NAC scavenging of ROS accumulation. Moreover, HA promoted bone formation and inhibited bone resorption in vitro. In conclusion, our findings suggest that HA may be an excellent candidate for treating breast cancer bone metastasis.


Asunto(s)
Neoplasias Óseas , Osteólisis , Animales , Ratones , Metaloproteinasa 9 de la Matriz , Especies Reactivas de Oxígeno , Metaloproteinasa 13 de la Matriz , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/metabolismo , Línea Celular Tumoral , Movimiento Celular , Metástasis de la Neoplasia
8.
J Med Virol ; 94(10): 5051-5055, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35729074

RESUMEN

The coronavirus disease 2019 (COVID-19) pandemic caused by the coronavirus severe acute respiratory syndrome coronavirus 2 remains risky worldwide. We elucidate here that good IDM (isolation, disinfection, and maintenance of health) is powerful to reduce COVID-19 deaths based on the striking differences in COVID-19 case fatality rates among various scenarios. IDM means keeping COVID-19 cases away from each other and from other people, disinfecting their living environments, and maintaining their health through good nutrition, rest, and treatment of symptoms and pre-existing diseases (not through specific antiviral therapy). Good IDM could reduce COVID-19 deaths by more than 85% in 2020 and more than 99% in 2022. This is consistent with the fact that good IDM can minimize co-infections and maintain body functions and the fact that COVID-19 has become less pathogenic (this fact was supported with three novel data in this report). Although IDM has been frequently implemented worldwide to some degree, IDM has not been highlighted sufficiently. Good IDM is relative, nonspecific, flexible, and feasible in many countries, and can reduce deaths of some other relatively mild infectious diseases. IDM, vaccines, and antivirals aid each other to reduce COVID-19 deaths. The IDM concept and strategy can aid people to improve their health behavior and fight against COVID-19 and future pandemics worldwide.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Antivirales/uso terapéutico , Humanos , Pandemias/prevención & control , SARS-CoV-2
9.
J Med Virol ; 94(6): 2388-2401, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35072274

RESUMEN

The newly established virus family Phenuiviridae in Bunyavirales harbors viruses infecting three kingdoms of host organisms (animals, plants, and fungi), which is rare in known virus families. Many phenuiviruses are arboviruses and replicate in two distinct hosts (e.g., insects and humans or rice). Multiple phenuivirid species, such as Dabie bandavirus, Rift Valley fever phlebovirus, and Rice stripe tenuivirus, are highly pathogenic to humans, animals, or plants. They impose heavy global burdens on human health, livestock industry, and agriculture and are research hotspots. In recent years the taxonomy of Phenuiviridae has been expanded greatly, and research on phenuiviruses has made significant progress. With these advances, this review drew a novel panorama regarding the biomedical significance, distribution, morphology, genomics, taxonomy, evolution, replication, transmission, pathogenesis, and control of phenuiviruses, to aid researchers in various fields to recognize this highly adaptive and important virus family and conduct relevant risk analysis.


Asunto(s)
Arbovirus , Phlebovirus , Virus ARN , Animales , Genómica , Humanos
10.
Chem Rev ; 120(20): 11194-11294, 2020 10 28.
Artículo en Inglés | MEDLINE | ID: mdl-32915551

RESUMEN

Hierarchical zeolites combine the intrinsic catalytic properties of microporous zeolites and the enhanced access and transport of the additional meso- and/or macroporous system. These materials are the most desirable catalysts and sorbents for industry and become a highly evolving field of important current interests. In addition to the enhanced mass transfer leading to high activity, selectivity, and cycle time, another essential merit of the hierarchical structure in zeolite materials is that it can significantly improve the utilization effectiveness of zeolite materials resulting in the minimum energy, time, and raw materials consumption. Substantial progress has been made in the synthesis, characterization, and application of hierarchical zeolites. Herein, we provide an overview of recent achievements in the field, highlighting the significant progress in the past decade on the development of novel and remarkable strategies to create an additional pore system in zeolites. The most innovative synthesis approaches are reviewed according to the principle, versatility, effectiveness, and degree of reality while establishing a firm link between the preparation route and the resultant hierarchical pore quality in zeolites. Zeolites with different hierarchically porous structures, i.e., micro-mesoporous structure, micro-macroporous structure, and micro-meso-macroporous structure, are then analyzed in detail with concrete examples to illustrate their benefits and their fabrications. The significantly improved performances in catalytic, environmental, and biological applications resulting from enhanced mass transport properties are discussed through a series of representative cases. In the concluding part, we envision the emergence of "material-properties-by-quantitative and real rational design" based on the "generalized Murray's Law" that enables the predictable and controlled productions of bioinspired hierarchically structured zeolites. This Review is expected to attract important interests from catalysis, separation, environment, advanced materials, and chemical engineering fields as well as biomedicine for artificial organ and drug delivery systems.


Asunto(s)
Dióxido de Carbono/aislamiento & purificación , Diseño de Fármacos , Compuestos Orgánicos Volátiles/aislamiento & purificación , Aguas Residuales/química , Contaminantes Químicos del Agua/aislamiento & purificación , Zeolitas/síntesis química , Adsorción , Dióxido de Carbono/química , Tamaño de la Partícula , Porosidad , Compuestos Orgánicos Volátiles/química , Contaminantes Químicos del Agua/química , Zeolitas/química
11.
Int J Mol Sci ; 24(1)2022 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-36613856

RESUMEN

The aim was to assess the protective effect of pioglitazone (PGZ) on retinal ganglion cells (RGCs) after anterior ischemic optic neuropathy (AION) in diabetic and non-diabetic mice. Adult C57BL/6 mice with induced diabetes were divided into three groups: group 1: oral PGZ (20 mg/kg) in 0.1% dimethyl sulfoxide (DMSO) for 4 weeks; group 2: oral PGZ (10 mg/kg) in 0.1% DMSO for 4 weeks; and group 3: oral DMSO only for 4 weeks (control group). Two weeks after treatment, AION was induced through photochemical thrombosis. For non-diabetic mice, adult C57BL/6 mice were divided into four groups after AION was induced: group 1: oral DMSO for 4 weeks; group 2: oral PGZ (20 mg/kg) in 0.1% DMSO for 4 weeks; group 3: oral PGZ (20 mg/kg) in 0.1% DMSO + peritoneal injection of GW9662 (one kind of PPAR-γ inhibitor) (1 mg/kg) for 4 weeks; group 4: peritoneal injection of GW9662 (1 mg/kg) for 4 weeks; One week after the induction of AION in diabetic mice, apoptosis in RGCs was much lower in group 1 (8.0 ± 4.9 cells/field) than in group 2 (24.0 ± 11.5 cells/field) and 3 (25.0 ± 7.7 cells/field). Furthermore, microglial cell infiltration in the retina (group 1: 2.0 ± 2.6 cells/field; group 2: 15.6 ± 3.5 cells/field; and group 3: 14.8 ± 7.5 cells/field) and retinal thinning (group 1: 6.7 ± 5.7 µm; group 2: 12.8 ± 6.1 µm; and group 3: 15.8 ± 5.8 µm) were also lower in group 1 than in the other two groups. In non-diabetic mice, preserved Brn3A+ cells were significantly greater in group 2 (2382 ± 140 Brn3A+ cells/mm2, n = 7) than in group 1 (1920 ± 228 Brn3A+ cells/mm2; p = 0.03, n = 4), group 3 (1938 ± 213 Brn3A+ cells/mm2; p = 0.002, n = 4), and group 4 (2138 ± 126 Brn3A+ cells/mm2; p = 0.03, n = 4), respectively; PGZ confers protection to RGCs from damage caused by ischemic optic neuropathy in diabetic and non-diabetic mice.


Asunto(s)
Disco Óptico , Neuropatía Óptica Isquémica , Ratones , Animales , Células Ganglionares de la Retina , Neuropatía Óptica Isquémica/tratamiento farmacológico , Pioglitazona/farmacología , Dimetilsulfóxido , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad
12.
BMC Ophthalmol ; 21(1): 246, 2021 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-34088299

RESUMEN

PURPOSE: To investigate the accuracy of a newly developed, eye-tracking virtual reality (VR)-based ocular deviation measurement system in strabismus patients. METHODS: A VR-based ocular deviation measurement system was designed to simulate the alternative prism cover test (APCT). A fixation target was made to alternate between two screens, one in front of each eye, to simulate the steps of a normal prism cover test. Patient's eye movements were recorded by built-in eye tracking. The angle of ocular deviation was compared between the APCT and the VR-based system. RESULTS: This study included 38 patients with strabismus. The angle of ocular deviation measured by the VR-based system and the APCT showed good to excellent correlation (intraclass correlation coefficient, ICC = 0.897 (range: 0.810-0.945)). The 95% limits of agreement was 11.32 PD. Subgroup analysis revealed a significant difference between esotropia and exotropia (p < 0.001). In the esotropia group, the amount of ocular deviation measured by the VR-based system was greater than that measured by the APCT (mean = 4.65 PD), while in the exotropia group, the amount of ocular deviation measured by the VR-based system was less than that of the APCT (mean = - 3.01 PD). The ICC was 0.962 (range: 0.902-0.986) in the esotropia group and 0.862 (range: 0.651-0.950) in the exotropia group. The 95% limits of agreement were 6.62 PD and 11.25 PD in the esotropia and exotropia groups, respectively. CONCLUSIONS: This study reports the first application of a consumer-grade and commercial-grade VR-based device for assessing angle of ocular deviation in strabismus patients. This device could provide measurements with near excellent correlation with the APCT. The system also provides the first step to digitize the strabismus examination, as well as the possibility for its application in telemedicine.


Asunto(s)
Esotropía , Exotropía , Estrabismo , Realidad Virtual , Tecnología de Seguimiento Ocular , Humanos
13.
Phytother Res ; 35(8): 4347-4362, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34152633

RESUMEN

The VEGF/SphK1/S1P pathway is closely related to angiogenesis in rheumatoid arthritis (RA), but the precise underlying mechanisms are unclear at present. Here, we explored the involvement of the VEGF/SphK1/S1P cascade in RA models and determined the effects of GE intervention. Our results showed abnormal expression of proteins related to this pathway in RA synovial tissue. Treatment with GE effectively regulated the signal axis, inhibited angiogenesis, and alleviated RA symptoms. In vitro, TNF-ɑ enhanced the VEGF/SphK1/S1P pathway in a co-culture model of fibroblast-like synoviocytes (FLS) and vascular endothelial cells (VEC). GE induced downregulation of VEGF in FLS, restored the dynamic balance of pro-/antiangiogenic factors, and suppressed SphK1/S1P signaling in VEC, resulting in lower proliferation activity, migration ability, tube formation ability, and S1P secretion ability of VEC cells. Additionally, SphK1-specific small interfering RNA (siRNA) blocked the VEGF/SphK1/S1P cascade, which can effectively alleviate the stimulatory effect of FLS on VEC and further enhanced the therapeutic effect of GE. Taken together, our results demonstrate that GE suppresses the VEGF/SphK1/S1P pathway and alleviates the stimulation of VEC by FLS, thereby preventing angiogenesis and promoting therapeutic effects against RA.


Asunto(s)
Artritis Reumatoide , Iridoides/farmacología , Neovascularización Patológica/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Proteínas Adaptadoras Transductoras de Señales , Artritis Reumatoide/tratamiento farmacológico , Proliferación Celular , Células Cultivadas , Células Endoteliales , Fibroblastos , Humanos , Receptores de Esfingosina-1-Fosfato , Membrana Sinovial , Factor A de Crecimiento Endotelial Vascular
14.
Horm Metab Res ; 52(5): 316-321, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32403146

RESUMEN

The aim of the study was to evaluate the remission rate with short-term premixed insulin therapy in newly diagnosed type 2 diabetes outpatients and investigate predictors contributing to the remission rate. A 5-year prospective study was conducted with a total of 170 patients enrolled. Patients were treated with premixed insulin monotherapy or insulin in combination with one or two oral drugs. After glucose levels were well controlled, insulin and oral drugs were discontinued in a stepwise manner. The prolonged and partial remission rates were calculated and the possible factors contributing to remission were also analyzed. A total of 164 subjects completed the research study. The prolonged remission, partial remission and non-remission rates at the 5-year follow-up were 9.8, 59.8, and 30.5%, respectively. The remission rate was negatively correlated with disease duration (r=0.39). The combined rate of remission (prolonged and partial remission) significantly decreased when the duration was longer than 16 days, and reduced to approximately 50% after 1 month. Moreover, 75% of prolonged remission patients had duration of < 16 days. At the 5-year follow-up, the prolonged remission rate was 9.8% and the partial remission rate was 59.8%. Furthermore, the duration after diagnosis is an independent predictor of remission rate, and initiation of short-term premixed insulin therapy within the first 16 days of diabetes diagnosis is very important for remission. This is the first study to evaluate the remission rate associated with short-term premixed insulin therapy in recently diagnosed type 2 diabetes outpatients. At the 5-year follow-up, the prolonged remission rate was 9.8% and the partial remission rate was 59.8%. The duration of diabetes was identified as an independent predictor of drug-free remission. The initiation of short-term premixed insulin therapy within 15 days of diabetes onset is particular importance for remission.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Pacientes Ambulatorios , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Inducción de Remisión
15.
Lipids Health Dis ; 19(1): 150, 2020 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-32580730

RESUMEN

BACKGROUND: Inflammation and oxidative stress play predominant roles in the initiation and progression of ischaemia/reperfusion (I/R) injury, with nuclear factor kappa B (NF-κB) serving as a crucial mediator. Overexpression of the inhibitor of κB alpha (IκBα) gene is hypothesized to have protective effects against apoptosis and autophagy in cardiomyocytes subjected to hydrogen peroxide (H2O2) by inhibiting the NF-κB pathway. METHODS: The IκBαS32A, S36A gene was transfected via adeno-associated virus serotype 9 (AAV9) delivery into neonatal rat ventricular cardiomyocytes (NRVMs) prior to H2O2 treatment. NRVMs were divided into control, H2O2, GFP + H2O2, IκBα+H2O2, and pyrrolidine dithiocarbamate (PDTC) + H2O2 groups. Nuclear translocation of the NF-κB p65 subunit was evaluated by immunofluorescence and Western blotting. Cell viability was assessed by Cell Counting Kit-8 assay. Supernatant lactate dehydrogenase (LDH) and intracellular malondialdehyde (MDA) were measured to identify H2O2-stimulated cytotoxicity. Apoptosis was determined by Annexin V-PE/7-AAD staining, and the mitochondrial membrane potential (ΔΨm) was detected by JC-1 staining. Western blotting was used to detect apoptosis- and autophagy-related proteins. RESULTS: IκBα transfection significantly increased cell viability and ΔΨm but decreased the supernatant LDH and cellular MDA levels in cardiomyocytes exposed to H2O2. Meanwhile, IκBα overexpression decreased H2O2-induced apoptosis by upregulating the Bcl-2/Bax ratio and reduced autophagy by downregulating the expression of Beclin-1 and the LC3-II/LC3-I ratio. These effects partly accounted for the ability of IκBα to inhibit the NF-κB signalling pathway, as evidenced by decreases in p65 phosphorylation and nuclear translocation. Indeed, the effects of inactivation of NF-κB signalling with the specific inhibitor PDTC resembled the cardioprotective effects of IκBα during H2O2 stimulation. CONCLUSION: IκBα overexpression can ameliorate H2O2-induced apoptosis, autophagy, oxidative injury, and ΔΨm loss through inhibition of the NF-κB signalling pathway. These findings suggest that IκBα transfection can result in successful resistance to oxidative stress-induced damage by inhibiting NF-κB activation, which may provide a potential therapeutic target for the prevention of myocardial I/R injury.


Asunto(s)
Peróxido de Hidrógeno/farmacología , Miocitos Cardíacos/patología , Inhibidor NF-kappaB alfa/genética , FN-kappa B/metabolismo , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Autofagia/efectos de los fármacos , Autofagia/genética , Células Cultivadas , Dependovirus/genética , Regulación de la Expresión Génica , Peróxido de Hidrógeno/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Inhibidor NF-kappaB alfa/metabolismo , FN-kappa B/antagonistas & inhibidores , FN-kappa B/genética , Pirrolidinas/farmacología , Ratas Sprague-Dawley , Tiocarbamatos/farmacología , Transfección
16.
Angew Chem Int Ed Engl ; 59(44): 19582-19591, 2020 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-32643251

RESUMEN

Zeolite Beta single crystals with intracrystalline hierarchical porosity at macro-, meso-, and micro-length scales can effectively overcome the diffusion limitations in the conversion of bulky molecules. However, the construction of large zeolite Beta single crystals with such porosity is a challenge. We report herein the synthesis of hierarchically ordered macro-mesoporous single-crystalline zeolite Beta (OMMS-Beta) with a rare micron-scale crystal size by an in situ bottom-up confined zeolite crystallization strategy. The fully interconnected intracrystalline macro-meso-microporous hierarchy and the micron-sized single-crystalline nature of OMMS-Beta lead to improved accessibility to active sites and outstanding (hydro)thermal stability. Higher catalytic performances in gas-phase and liquid-phase acid-catalyzed reactions involving bulky molecules are obtained compared to commercial Beta and nanosized Beta zeolites. The strategy has been extended to the synthesis of other zeolitic materials, including ZSM-5, TS-1, and SAPO-34.

17.
Biochem Biophys Res Commun ; 512(1): 125-130, 2019 04 23.
Artículo en Inglés | MEDLINE | ID: mdl-30876692

RESUMEN

Oxidative stress injury is one of the main mechanisms of ischemia-reperfusion (I/R) injury. The extracellular signal-regulated kinase (ERK1/2) pathway plays an important role in cardioprotective during acute myocardial infarction. In this study, we used constitutively active MEK1 gene (CaMEK) transfection strategy to investigate whether CaMEK provides a protective effect against apoptosis and autophagy induced by Hydrogen peroxide (H2O2) in neonatal rat cardiac ventricular cardiomyocytes (NCMs) and the underlying mechanisms. As a result, CaMEK attenuated H2O2-induced apoptosis and cytotoxicity in NCMs, evidenced by decreased apoptotic cells and the ratio of Bax/Bcl-2, increased the mitochondrial membrane potential (Δψm) and cell vitality and reduced the level of lactate dehydrogenase (LDH). Further studies revealed that CaMEK attenuated H2O2-induced autophagy, evidenced by the decreased LC3-Ⅱ/LC3-Ⅰratio and SQSTM1/p62 (p62) degradation. Furthermore, we demonstrated that CaMEK phosphorylated the ERK1/2 pathway-related proteins, ERK1/2, p70S6K and GSK3ß, in NCMs with H2O2 stimulation. In contrast, these effects could be reversed by co-treatment with the ERK1/2 inhibitor, PD98059. These results suggest that CaMEK plays an important role in protecting cardiomyocytes against H2O2-induced injury and autophagy in NCMs via ERK1/2 pathway. Therefore, transfection of CaMEK may provide a hopeful therapeutic strategy for I/R.


Asunto(s)
MAP Quinasa Quinasa 1/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Animales , Animales Recién Nacidos , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Cardiotónicos/metabolismo , Células Cultivadas , Femenino , Peróxido de Hidrógeno/toxicidad , MAP Quinasa Quinasa 1/genética , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Miocitos Cardíacos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transfección
19.
Entropy (Basel) ; 21(5)2019 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-33267251

RESUMEN

Machine learning techniques have shown superior predictive power, among which Bayesian network classifiers (BNCs) have remained of great interest due to its capacity to demonstrate complex dependence relationships. Most traditional BNCs tend to build only one model to fit training instances by analyzing independence between attributes using conditional mutual information. However, for different class labels, the conditional dependence relationships may be different rather than invariant when attributes take different values, which may result in classification bias. To address this issue, we propose a novel framework, called discriminatory target learning, which can be regarded as a tradeoff between probabilistic model learned from unlabeled instance at the uncertain end and that learned from labeled training data at the certain end. The final model can discriminately represent the dependence relationships hidden in unlabeled instance with respect to different possible class labels. Taking k-dependence Bayesian classifier as an example, experimental comparison on 42 publicly available datasets indicated that the final model achieved competitive classification performance compared to state-of-the-art learners such as Random forest and averaged one-dependence estimators.

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