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1.
Int Immunopharmacol ; 131: 111912, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38522140

RESUMEN

Water-soluble rhamnogalacturonan-I enriched citrus pectin (WRP) has promising effect on antimicrobial defense. We aim to determine whether the modified acidic (A) or neutral (B) WRP solutions can improve intestinal microbial dysbiosis in burn-injured mice. Male Balb/c mice were gavaged with WRPs at 80, 160, 320 mg/kg. Body weight daily for 21 days before exposed to thermal injury of 15 % total body surface area and mortality was monitored. Mice with 80 mg/kg WRPs were also subjected to fecal DNAs and T cell metabonomics analysis, intestinal and plasma glucagon-like peptide 1 (GLP-1) detection, plasma defensin, immunoglobin and intestinal barrier examinations at 1 and 3d postburn (p.b.). Burn-induced mortality was only improved by low dose WRP-A (P = 0.039). Both WRPs could prevent the dysbiosis of gut microbiota in burn injury by reducing the expansion of inflammation-promoting bacteria. Both WRPs suppressed ileum GLP-1 production at 1d p.b. (P = 0.002) and plasma GLP-1 levels at 3d p.b. (P = 0.013). Plasma GLP-1 level correlated closely with ileum GLP-1 production (P = 0.019) but negatively with microbiota diversity at 1d p.b. (P = 0.003). Intestinal T cell number was increased by both WRPs in jejunum at 3d p.b. However, the exaggerated splenic T cell metabolism in burn injury was reversed by both WRPs at 1d p.b. The burn-increased plasma defensin ß1 level was only reduced by WRP-B. Similarly, the intestinal barrier permeability was only rescued by WRP-B at 1d p.b. WRP-A rather than WRP-B could reduce burn-induced mortality in mice by suppressing intestinal GLP-1 secretion, restoring gut microbiota dysbiosis and improving adaptive immune response.


Asunto(s)
Quemaduras , Microbioma Gastrointestinal , Pectinas , Ratones , Masculino , Animales , Péptido 1 Similar al Glucagón , Disbiosis/tratamiento farmacológico , Inmunidad , Quemaduras/tratamiento farmacológico , Quemaduras/metabolismo , Defensinas
2.
J Cardiothorac Surg ; 19(1): 101, 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38374106

RESUMEN

BACKGROUND: Acupuncture, a traditional Chinese medical treatment, has been gaining popularity over the years. However, it also presents certain risks. We report a case of a patient who discovered a foreign body in their lung several years after undergoing acupuncture. CASE PRESENTATION: A middle-aged woman presented to our hospital with chest pain. An X-ray revealed a needle-like foreign body in the middle lobe of her right lung. The patient had previously undergone acupuncture treatment for local pain in her lower back and lower extremities many years prior. Based on the imaging findings and her medical history, we hypothesized that the foreign body in her lung was a result of a dislodged acupuncture needle. Through preoperative 3-dimensional reconstruction and indocyanine green localization, we were able to locate the foreign body in the lateral segment of the right middle lobe. We successfully removed the foreign body via wedge resection, and the patient made a smooth recovery post-surgery. CONCLUSION: Acupuncturists and surgeons should remain vigilant about the potential risks associated with acupuncture.


Asunto(s)
Terapia por Acupuntura , Cuerpos Extraños , Migración de Cuerpo Extraño , Humanos , Persona de Mediana Edad , Femenino , Agujas/efectos adversos , Terapia por Acupuntura/efectos adversos , Cuerpos Extraños/diagnóstico por imagen , Cuerpos Extraños/etiología , Cuerpos Extraños/cirugía , Radiografía , Dolor en el Pecho , Migración de Cuerpo Extraño/diagnóstico por imagen , Migración de Cuerpo Extraño/etiología
3.
Xenobiotica ; 53(12): 670-680, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37971898

RESUMEN

Maintaining proper blood flow is critical to promoting good health. Nattokinase is a serine protease from Bacillus subtilis that has significant in vitro thrombolytic activity, but its mechanism as a dietary supplement to prevent thrombosis through intestinal absorption and transport is still unclear.The purpose of this study is to study the transport and internalisation mechanism of NK in the small intestine using animal models and Caco-2 cell monolayer models.This study first evaluated the preventive effect of supplementing low dose (4000 FU (Fibrin Unit)/kg, n = 6), medium dose (8000 FU/kg, n = 6), and high dose (12000 FU/kg, n = 6) of nattokinase on carrageenan induced thrombosis in mice. Subsequently, we used the rat gut sac model, ligated intestinal loop model, and Caco-2 cell uptake model to study the intestinal transport mechanism of NK.Results indicate that NK is a moderately absorbed biomolecule whose transport through enterocytes is energy- and time-dependent. Chlorpromazine, nystatin and EIPA all inhibited the endocytosis of NK to varying degrees, indicating that the endocytosis of NK in Caco-2 cells involves macropinocytosis, clathrin-mediated and caveolae-mediated pathway. These findings offer a theoretical basis for investigating the mechanism of oral NK supplementation in greater depth.


Asunto(s)
Intestino Delgado , Trombosis , Humanos , Ratas , Ratones , Animales , Células CACO-2 , Suplementos Dietéticos
4.
Foods ; 10(7)2021 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-34359425

RESUMEN

Casein phosphopeptide (CPP) has been widely used as micronutrient supplementation for certain populations. However, its solubility performance is far from satisfying. In this work, instant CPP powders with micropore structures were fabricated by supercritical fluid-assisted atomization (SAA) using supercritical CO2 fluid (SC-CO2) as an atomizing agent. The effects of the processing parameters (temperature, time, and pressure) on SC-CO2 absorption rate and dissolution rate were systematically evaluated and studied. The viscosity of the CPP solution increased with increased pressure of SC-CO2 as pressure increased its solubility. The processing conditions are optimized as follows: 40 °C, 40 min, and 8.27 MPa, with an SC-CO2 absorption rate of about 8 wt.%. The dissolution time of the SAA-CPP powders was significantly decreased from 1800 s to 54 s at room temperature, due to the micropore structures and almost 10 times increase in the specific surface area of SAA-CPP. The bioactivities of the instant SAA-CPP, especially the calcium-binding capacity, were also evaluated and showed no observable difference. Among the four CPPs prepared in different ways in this work, SAA-CPP had better dissolution performance. The results show that SAA technology is a promising way to prepare instant polypeptide powders.

5.
Carbohydr Polym ; 272: 118450, 2021 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-34420712

RESUMEN

One of the well-recognized weaknesses of starch-based materials is their sensitivity to moisture, which limits their expanding applications. Natural materials, soyabean oils have been used as a coating for starch film, but the poor interface between hydrophilic starch and hydrophobic soyabean oil needs to be improved. In this work, (3-Aminopropyl) triethoxysilane (APTES) was used to reinforce the bonding between starch matrix and the coating of bio-based acrylated epoxidized soyabean oil (AESO). Study results show that APTES interacted effectively with both starch films via hydrogen bonding, and chemical bonds with AESO through the Michael addition reaction. Pull adhesion and cross-cutting tests demonstrated that the interfacial adhesion was significantly improved after treating their surface with APTES. The interfacial adhesion strength increased over 4 times after treating with 1.6 wt% APTES. The starch films treated with APTES and AESO coating were intact after soaking in water for more than 2 h.


Asunto(s)
Interacciones Hidrofóbicas e Hidrofílicas , Propilaminas/química , Silanos/química , Aceite de Soja/química , Almidón/química , Enlace de Hidrógeno , Microscopía Electrónica de Rastreo/métodos , Permeabilidad , Espectroscopía de Fotoelectrones/métodos , Aceites de Plantas/química , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Agua/química
6.
Int J Nanomedicine ; 15: 9759-9770, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33304100

RESUMEN

BACKGROUND: Delivery of therapeutic small interfering RNA (siRNA) via functionalized nanoparticles holds great promise for cancer therapy. However, developing a safe and efficient delivery carrier of siRNA is a challenging issue. METHODS: RGDfC peptide was used to modify the surface of selenium nanoparticles (SeNPs) to synthesize a biocompatible siRNA delivery vehicle (R-SeNPs), and MEF2D-siRNA was loaded onto R-SeNPs to prepare a functionalized selenium nanoparticle R-Se@MEF2D-siRNA. The chemical properties of R-SeNPs were characterized, and the anticancer efficacy as well as related mechanisms of R-Se@MEF2D-siRNA were further explored. RESULTS: R-Se@MEF2D-siRNA was significantly taken up by SKOV3 cells and could enter SKOV3 cells mainly in the clathrin-associated endocytosis way. The result of in vitro siRNA release demonstrated that R-Se@MEF2D-siRNA could release MEF2D-siRNA quicker in a microenvironment simulating a lysosomal environment in tumor cells compared to a normal physiological environment. The results of qRT-PCR assay proved that R-Se@MEF2D-siRNA could effectively silence the expression of the MEF2D gene in SKOV3 cells. R-Se@MEF2D-siRNA remarkably suppressed the proliferation of SKOV3 cells and further triggered its apoptosis. In addition, R-Se@MEF2D-siRNA had the capability to disrupt mitochondrial membrane potential (MMP) in SKOV3 cells and resulted in the overproduction of reactive oxygen species (ROS), indicating that mitochondrial dysfunction and ROS generation played an important role in the apoptosis of SKOV3 cells induced by R-Se@MEF2D-siRNA. In vivo, R-Se@MEF2D-siRNA also exhibited excellent antitumor activity mainly through decreasing tumor cells proliferation and triggering their apoptosis in tumor-bearing nude mice. CONCLUSION: R-Se@MEF2D-siRNA provides an alternative strategy for ovarian cancer treatment in the clinic.


Asunto(s)
Silenciador del Gen , Nanopartículas/química , Neoplasias Ováricas/terapia , ARN Interferente Pequeño/química , ARN Interferente Pequeño/genética , Selenio/química , Animales , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular/genética , Portadores de Fármacos/química , Femenino , Humanos , Factores de Transcripción MEF2/deficiencia , Factores de Transcripción MEF2/genética , Ratones , Ratones Desnudos , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Especies Reactivas de Oxígeno/metabolismo , Microambiente Tumoral/genética
7.
Mater Sci Eng C Mater Biol Appl ; 110: 110594, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32204058

RESUMEN

Short interfering RNA (siRNA) has been investigated as a promising modality of cancer treatment due to its capability to target specific target genes for downregulation. However, the successful application of this strategy depends on producing a safe and effective carrier system for delivering siRNA to the tumor. Thus, investigation of siRNA delivery carriers is a fundamental step in the field of siRNA-based therapeutics. In the current research, the surface of selenium nanoparticles (SeNPs) were modified with the tumor-targeted molecular RGDfC peptide with positive charge to synthetize the biocompatible siRNA carrier RGDfC-SeNPs. Subsequently, KLK12-siRNA was loaded onto the surface of RGDfC-SeNPs to create functionalized nanoparticles (RGDfC-Se@siRNA) that we tested for in vitro and in vivo antitumor efficacy. We measured significantly greater particle uptake in HT-29 colorectal cancer cells relative to HUVECs, providing evidence for the targeted delivery of RGDfC-Se@siRNA. We found that RGDfC-Se@siRNA could enter HT-29 cells primarily via clathrin-mediated endocytosis. Further, these particles experienced faster siRNA release in an acidic microenvironment compared to pH 7.4. The results from quantitative PCR and Western blot assays suggested that the target gene of KLK12 in HT-29 cells were obviously silenced by RGDfC-Se@siRNA. The further biological studies showed that treatment with RGDfC-Se@siRNA had ability to suppress the proliferation and migration/invasion of HT-29 cells, and triggered HT-29 cells apoptosis. RGDfC-Se@siRNA could induce the mitochondrial membrane potential (MMP) disruption and enhance the reactive oxygen species (ROS) generation in HT-29 cells, indicating that RGDfC-Se@siRNA induced the HT-29 cells apoptosis possibly by a ROS-mediated mitochondrial dysfunction pathway. Importantly, the in vivo antitumor study also verified that RGDfC-Se@siRNA could significantly suppress the growth of tumor in vivo. In addition, we did not observe any signs of systemic or tissue-specific toxicity after administration of RGDfC-Se@siRNA in mice. As a whole, these findings suggest that RGDfC-Se@siRNA has promising potential as a therapy for colorectal cancer.


Asunto(s)
Neoplasias Colorrectales , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Silenciador del Gen/efectos de los fármacos , Calicreínas/biosíntesis , Nanopartículas del Metal , Proteínas de Neoplasias/biosíntesis , Oligopéptidos , Selenio , Animales , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/patología , Femenino , Células HT29 , Células Endoteliales de la Vena Umbilical Humana , Humanos , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Oligopéptidos/química , Oligopéptidos/farmacología , Selenio/química , Selenio/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto
8.
J Mater Chem B ; 8(2): 251-259, 2020 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-31799596

RESUMEN

To create a more precise, efficient imaging and therapeutic strategy is a big challenge for the current treatment of hepatocellular carcinoma (HCC). Photothermal therapy (PTT) has attracted enormous attention due to its non-invasive property and precise spatial and temporal control. Here, we developed a strategy to realize superior imaging performance and treatment, utilizing an indocyanine green (ICG) and sorafenib (S) co-loaded mesoporous silica nanosystem for synergetic PTT/immuno-enhanced therapy. We proved that (ICG+S)@mSiO2 could be easily endocytosed by H22 cells, carried out outstanding real-time fluorescence imaging, and enhanced cytotoxicity abilities by near-infrared radiation (NIR) in vitro. Moreover, (ICG+S)@mSiO2 also had excellent fluorescence imaging ability, displayed a remarkable photothermal tumor killing effect and immune enhancement capability under 808 nm irradiation in an H22 tumor-bearing mice model, without apparent adverse effects in other organs. This study provides a new strategy for the development of a PTT/immuno-enhanced synergistic theranostic nanosystem of HCC.


Asunto(s)
Carcinoma Hepatocelular/tratamiento farmacológico , Inmunoterapia/métodos , Neoplasias Hepáticas/tratamiento farmacológico , Nanopartículas/uso terapéutico , Fototerapia/métodos , Nanomedicina Teranóstica/métodos , Animales , Antineoplásicos/administración & dosificación , Línea Celular Tumoral , Femenino , Verde de Indocianina , Ratones , Ratones Endogámicos C57BL , Dióxido de Silicio , Sorafenib/administración & dosificación
9.
Drug Deliv ; 27(1): 15-25, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31830840

RESUMEN

Small interfering RNA (siRNA) exhibits great potential as a novel therapeutic option due to its highly sequence-specific ability to silence genes. However, efficient and safe delivery carriers are required for developing novel therapeutic paradigms. Thus, the successful development of efficient delivery platforms for siRNA is a crucial issue for the development of siRNA-based drugs in cancer treatments. In this study, biocompatible selenium nanoparticles (SeNPs) were loaded with RGDfC peptide to fabricate tumor-targeting gene delivery vehicle RGDfC-SeNPs. Subsequently, RGDfC-SeNPs were loaded with Derlin1-siRNA to fabricate RGDfC-Se@siRNA, which are functionalized selenium nanoparticles. RGDfC-Se@siRNA showed greater uptake in HeLa cervical cancer cells in comparison with that in human umbilical vein endothelial cells (HUVECs), verifying the RGDfC-mediated specific uptake of RGDfC-Se@siRNA. RGDfC-Se@siRNA was capable of entering HeLa cells via clathrin-associated endocytosis, and showed faster siRNA release in a cancer cell microenvironment in comparison with a normal physiological environment. qPCR and western blotting assays both indicated that RGDfC-Se@siRNA exhibited an obvious gene silencing efficacy in HeLa cells. RGDfC-Se@siRNA suppressed the invasion, migration and the proliferation of HeLa cells, and triggered HeLa cell apoptosis. Moreover, RGDfC-Se@siRNA induced the disruption of mitochondrial membrane potentials. Meanwhile, RGDfC-Se@siRNA enhanced the generation of reactive oxygen species (ROS) in HeLa cell, suggesting that mitochondrial dysfunction mediated by ROS might play a significant role in RGDfC-Se@siRNA-induced apoptosis. Interestingly, RGDfC-SeNPs@siRNA exhibited significant antitumor activity in a HeLa tumor-bearing mouse model. Additionally, RGDfC-SeNPs@siRNA is nontoxic to main organ of mouse. The above results indicate that RGDfC-Se@siRNA provides a promising potential for cervical cancer therapy.


Asunto(s)
Proteínas de la Membrana/efectos de los fármacos , Nanopartículas/química , Oligopéptidos/farmacología , ARN Interferente Pequeño/administración & dosificación , Selenio/química , Apoptosis/efectos de los fármacos , Western Blotting , Inhibición de Migración Celular , Proliferación Celular/efectos de los fármacos , Femenino , Silenciador del Gen/efectos de los fármacos , Células HeLa , Células Endoteliales de la Vena Umbilical Humana , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Oligopéptidos/administración & dosificación , Oligopéptidos/farmacocinética , Especies Reactivas de Oxígeno/metabolismo , Microambiente Tumoral , Neoplasias del Cuello Uterino/tratamiento farmacológico
10.
Mater Sci Eng C Mater Biol Appl ; 106: 110100, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31753388

RESUMEN

Development of novel tumor-targeted drug vehicles for cancer therapy is very important and has become one of major topics for designing nanoscale chemotherapeutics delivery systems. In the present study, selenium nanoparticles (SeNPs) was decorated with hyaluronic acid (HA) to prepare HA-SeNPs nanoparticles which were used to load doxorubicin (DOX) to fabricate tumor-targeted functionalized selenium nanoparticles HA-Se@DOX. In vitro and in vivo antitumor activities of HA-Se@DOX in human cervical carcinoma treatment were investigated. HA-Se@DOX showed selective cellular uptakes between cervical cancer HeLa cells and human umbilical vein endothelial cells (HUVEC). In vitro release result indicated that DOX was released from HA-SeNPs faster in acidic environment in comparison with normal physiological environment and 76.9% DOX was released in pH 5.4 during initial 30 h. HA-Se@DOX showed high activity to inhibit HeLa cell proliferation and triggered HeLa cell apoptosis via activating Bcl-2 signaling pathway. In vivo antitumor study showed that HA-Se@DOX inhibited tumor growth through suppressing cancer cells proliferation and inducing cancer cells apoptosis. Interestingly, HA-Se@DOX exhibited stronger anticancer activity than free DOX and Se@DOX in vitro and in vivo. Additionally, HA-Se@DOX did not cause damage to major organs at the used dose. HA-Se@DOX is a promising antitumor agent for human cervical carcinoma treatment and this research provides a novel therapeutic strategy for cancer therapy.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Doxorrubicina/farmacología , Portadores de Fármacos/química , Nanopartículas/química , Animales , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/química , Doxorrubicina/uso terapéutico , Femenino , Células HeLa , Células Endoteliales de la Vena Umbilical Humana , Humanos , Ratones , Ratones Desnudos , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Selenio/química , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología , Ensayos Antitumor por Modelo de Xenoinjerto
11.
Neuroscience ; 406: 38-49, 2019 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-30849448

RESUMEN

Enhancing the migration and phagocytosis of microglial cells is of great significance for the reducing of the risk of the neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). The effect of mouse selenoprotein K (mSELENOK) on the migration and phagocytosis of BV2 microglial cells and its mechanism were studied. The results showed that the over-expression of mSELENOK can increase the migratory and phagocytic abilities of the microglial cells, while the knockdown of mSELENOK can decrease the migratory and phagocytic abilities of the cells. The cytosolic free Ca2+ level and inositol trisphosphate receptor (IP3R) mRNA transcript and protein expression were also increased significantly as the consequence of the over-expression of mSELENOK in the microglial cells. On the contrary, the level of cytosolic free Ca2+ and the mRNA transcript and protein expression of IP3R in mSELENOK knockdown cells were decreased significantly. 2-aminoethoxydiphenyl borate (2-APB), an antagonist of IP3R, could prevent the increased migration, phagocytosis, and cytosolic free Ca2+ level of mSELENOK over-expressed microglial cells, and knockdown of IP3R3 could reduce the increased cytosolic Ca2+ level in mSELENOK over-expressed microglial cells. Further studies revealed that selenium supplement (Na2SeO3) can increase the expression of mSELENOK in microglial cells significantly. In summary, these data suggest that mSELENOK can increase cytosolic free Ca2+ level of microglial cells by up-regulating the expression of IP3R, thus enhancing the migration and phagocytosis of microglial cells. Our results indicated that mSELENOK is an important selenoprotein, which plays a role in trace element selenium's functions and can enhance the migration and phagocytosis of microglial cells.


Asunto(s)
Adenosilhomocisteinasa/biosíntesis , Movimiento Celular/fisiología , Citosol/metabolismo , Microglía/metabolismo , Fagocitosis/fisiología , Selenoproteínas/metabolismo , Animales , Calcio/metabolismo , Línea Celular , Supervivencia Celular/fisiología , Ratones , Regulación hacia Arriba/fisiología
12.
Int J Biol Macromol ; 125: 370-375, 2019 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-30508542

RESUMEN

Acrylated epoxidized soybean oil (AESO)-based coatings were developed to reduce moisture sensitivity and permeability of starch-based materials. The coating was applied on starch based films by dipping the samples on AESO-based coating solutions, followed by crosslinking with ultraviolet (UV) light. Effect of AESO concentration, photoinitiator content and processing conditions on the performance of coated starch-based film was systematically investigated, in particular the effect of coating on moisture absorption, permeability and mechanical properties. The modified surface was characterized by scanning electronic microscopy and Fourier transform infrared spectroscopy. The results showed that the moisture sensitivity of the starch-based sheets was reduced significantly since the crosslinked AESO acted as a hydrophobic layer. Moisture permeability was decreased more than 10 times after AESO treatment. It was found that the crosslinking density acted as one of the key factors, so even a very thin layer of AESO could achieve good water resistance.


Asunto(s)
Materiales Biocompatibles Revestidos/química , Membranas Artificiales , Aceite de Soja/química , Almidón/química , Fenómenos Químicos , Fenómenos Mecánicos , Permeabilidad , Análisis Espectral , Almidón/ultraestructura , Propiedades de Superficie , Agua
13.
Interdiscip Sci ; 10(2): 320-328, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29500549

RESUMEN

In recent years, new strains of influenza virus such as H7N9, H10N8, H5N6 and H5N8 had continued to emerge. There was an urgent need for discovery of new anti-influenza virus drugs as well as accurate and efficient large-scale inhibitor screening methods. In this study, we focused on six influenza virus proteins that could be anti-influenza drug targets, including neuraminidase (NA), hemagglutinin (HA), matrix protein 1 (M1), M2 proton channel (M2), nucleoprotein (NP) and non-structural protein 1 (NS1). Structure-based molecular docking was utilized to identify potential inhibitors for these drug targets from 13144 compounds in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The results showed that 56 compounds could inhibit more than two drug targets simultaneously. Further, we utilized reverse docking to study the interaction of these compounds with host targets. Finally, the 22 compound inhibitors could stably bind to host targets with high binding free energy. The results showed that the Chinese herbal medicines had a multi-target effect, which could directly inhibit influenza virus by the target viral protein and indirectly inhibit virus by the human target protein. This method was of great value for large-scale virtual screening of new anti-influenza virus compounds.


Asunto(s)
Antivirales/farmacología , Evaluación Preclínica de Medicamentos , Medicamentos Herbarios Chinos/farmacología , Medicina Tradicional China , Orthomyxoviridae/efectos de los fármacos , Humanos , Simulación del Acoplamiento Molecular , Neuraminidasa/química
14.
J Agric Food Chem ; 64(17): 3445-55, 2016 May 04.
Artículo en Inglés | MEDLINE | ID: mdl-27075043

RESUMEN

Aurantiamide and aurantiamide acetate are the main active constituents of purslane (Portulaca oleracea L.), an edible plant with various biological activities. In this study, we developed a validated UHPLC-MS/MS method to quantitate the concentrations of aurantiamide and aurantiamide acetate in the plasma and various organ tissues of rat as the basis to study their pharmacological profile and distribution in vivo. Aurantiamide and aurantiamide acetate were rapidly absorbed following oral administration, both achieving a Cmax at around 0.2 h. The extent of their metabolisms also varied among different organ tissues, resulting in about 90% reduction in concentrations 4 h after their administration, thus leaving no long-term accumulation in the tissues. This is the first study to examine the pharmacokinetic and biodistribution of aurantiamide and aurantiamide acetate in rat, and our work may serve as the first step toward the investigation of the underlying mechanisms associated with the biological activity of purslane.


Asunto(s)
Dipéptidos/farmacocinética , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacocinética , Portulaca/química , Administración Oral , Animales , Masculino , Ratas , Ratas Sprague-Dawley , Distribución Tisular
15.
FEMS Microbiol Ecol ; 91(5)2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25873463

RESUMEN

The current paradigm that stream producers are under exclusive macronutrient control was recently challenged by continental studies, demonstrating that iron supply constrained diatom biodiversity and energy flows. Using algal abundance and water chemistry data from the National Water-Quality Assessment Program, we determined for the first time community thresholds along iron gradients in non-acidic running waters, i.e. 30-79.5 µg L(-1) and 70-120 µg L(-1) in oligotrophic and eutrophic streams, respectively. Given that Fe concentrations fell below both thresholds in 50% of US streams, and below the eutrophic threshold in 75% of US streams, we suggest that Fe limitation is potentially widespread and attribute it to the restricted distribution of wetlands. We also report results from the first laboratory experiments on algal-iron interactions in streams, revealing that iron supplementation leads to significant biovolume and biodiversity increase in both nitrogen fixing and non-nitrogen fixing algae. Therefore, the progressive brownification of freshwaters due to rising dissolved organic carbon and iron levels can have a stimulating influence on microbial producers with cascading effects along the trophic hierarchy. Future research in running waters should focus on the role of iron in algal physiology and biofilm functions, including accumulation of biomass, fixing atmospheric nitrogen and improving water quality.


Asunto(s)
Cianobacterias/clasificación , Cianobacterias/metabolismo , Hierro/análisis , Hierro/metabolismo , Fijación del Nitrógeno/fisiología , Biodiversidad , Biopelículas/crecimiento & desarrollo , Biomasa , Diatomeas/metabolismo , Ecosistema , Eutrofización/fisiología , Agua Dulce/análisis , Nitrógeno/metabolismo , Ríos/química , Humedales
16.
J Pediatr Orthop B ; 24(1): 35-9, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25305044

RESUMEN

This study evaluates improvement of the acetabular index (AI) in patients with developmental dysplasia of the hip at 4 years after closed reduction, and determines the association between the final AI and a set of factors. Sixty-two patients (74 hips) treated with closed reduction were categorized into three groups according to age: group A (0-12 months, 18 hips), group B (13-18 months, 24 hips), and group C (>18 months, 32 hips). There was no difference in AI among the three groups before reduction (P=0.293). In groups A and C, the AI decreased significantly over time until 3 years after reduction and no differences were observed between the time points of 3 and 4 years. At 4 years after reduction, the AI of group C was significantly higher than that of groups A (P<0.001) and B (P=0.012). The overall AI improvement rate was 28.63%. The AI improvement rate of group A was significantly higher than that of group C (P=0.005). Pearson correlation analysis indicated no correlation between center-head distance discrepancy and the final AI (P=0.811). Linear regression suggested that age and initial AI correlated significantly with the final AI (R=0.617, F=15.031, P<0.001). Other factors, such as sex, center-edge angle of Wiberg, bilaterally involved, and avascular necrosis of the femoral head, showed no correlations with the final AI (P>0.05). According to the coefficients, initial AI (ß1=0.432, P<0.001) had greater effect than age (ß2=0.197, P=0.023) on the final AI. In conclusion, the AI decreases in all patients after reduction and stabilizes at 3 years after reduction. The AI improvement rate is correlated negatively with age. Age and initial AI are early predictors of the progress of AI after closed reduction in developmental dysplasia of the hip patients.


Asunto(s)
Acetábulo/crecimiento & desarrollo , Diagnóstico Tardío , Luxación Congénita de la Cadera/diagnóstico , Luxación Congénita de la Cadera/terapia , Manipulaciones Musculoesqueléticas/métodos , Análisis de Varianza , Femenino , Luxación Congénita de la Cadera/fisiopatología , Humanos , Lactante , Recién Nacido , Masculino , Análisis de Regresión , Estudios Retrospectivos
17.
Lipids Health Dis ; 13: 186, 2014 Dec 10.
Artículo en Inglés | MEDLINE | ID: mdl-25491404

RESUMEN

BACKGROUND: Atorvastatin and poly-unsaturated fatty acid (PUFA) are beneficial for lipid-modification, whether atorvastatin plus PUFA could confer better improvement on dyslipidemia and endothelium function is unknown. METHODS: Dyslipidemia model of 40 rabbits were produced with atherogenic diet, and thereafter saline, atorvastatin, PUFA, or atorvastatin plus PUFA were prescribed for 1 week. Ten rabbits given normal diet served as the sham group. Parameters of interest including lipid profiles, endothelium function (nitric oxide, NO) and activation (solution vascular-cellular adhesion molecule, (sVCAM) and intracellular adhesion molecule, (sICAM)), markers of inflammation (C-reactive protein, CRP) and oxidation (malondialdehyde, MDA) were compared among groups. RESULTS: There was no significant difference of parameters among groups at the initial. With 1 week of atherogenic diet administration, serum levels of lipid profiles, sVCAM and sICAM, CRP and MDA were significantly increased, accompanying with profound NO reduction, as compared to the sham group. After 1 week of medical intervention, as compared to the control group (saline administration), dyslipidemia and endothelium function were modestly improved with either atorvastatin or PUFA therapy. Nevertheless, these efficacies were further and significantly enhanced with combined therapy when compared to the control group (p<0.005), suggesting that there was synergistic effects of atorvastatin and PUFA co-therapy in rabbits with dyslipidemia. CONCLUSION: Atorvastatin plus PUFA therapy could immediately contribute to better improvement of lipid-modification and endothelium function in rabbits with dyslipidemia.


Asunto(s)
Anticolesterolemiantes/administración & dosificación , Dislipidemias/tratamiento farmacológico , Endotelio Vascular/fisiopatología , Ácidos Grasos Insaturados/administración & dosificación , Ácidos Heptanoicos/administración & dosificación , Pirroles/administración & dosificación , Animales , Atorvastatina , Evaluación Preclínica de Medicamentos , Quimioterapia Combinada , Dislipidemias/sangre , Endotelio Vascular/efectos de los fármacos , Masculino , Óxido Nítrico/sangre , Conejos
18.
Zhongguo Zhen Jiu ; 34(4): 329-33, 2014 Apr.
Artículo en Chino | MEDLINE | ID: mdl-24946628

RESUMEN

OBJECTIVE: To evaluate the clinical efficacy and efficacy sustainable time of acupuncture in knee osteoarthritis (KOA). METHODS: The non-randomized concurrent control trial was adopted. One hundred and ninety-three cases of KOA were divided into an immediate acupuncture group (group A, 97 cases) and a delayed acupunc-weeks at the end of treatment. In group B, the same acupuncture therapy was applied after waiting 4 weeks. The acupoints in the two groups were Liangqiu (ST 34), Dubi (ST 35), Zusanli (ST 36), Yanglingquan (GB 34), Yinlingquan (SP 9), Xuehai (SP 10), Xiyan (EX-LE 4), Xiyangguan (GB 33). WOMAC (Western Ontario and McMasters Universities Osteoarthritis) was used for the assessment of the primary index and VAS (visual analogue scale) was for the secondary index. The evaluation was accomplished by the patients at the beginning of trial, on the 4th and 8th weeks. In each group, 72 patients finished the trial and the data of the lost cases were included in the final data analysis. RESULTS: In the 4th week of trial, WOMAC score was (25. 8+/-22.0) in group A difference (P<0. 001). VAS scorewas (31. 8+/-24. and was (43.8+/-22.2) in group B, indicating the significant 6) in group A and was (56. 6 +/-25. 8) in group B, indicating very significant difference (P<0. 001). In the 8th week, the efficacy was reduced slightly in the follow-up of group A, but it was improved apparently as compared Acupuncture relieves joint pain and improves joint function obviously.by th patiieffr,a Mtaetfti-?an tf ri-with that before treatment. CONCLUSION: Acupuncture relieves joint pain and improves joint function obviously.The effect of acupuncture is still sustainable in 4 weeks after terminating the treatment.


Asunto(s)
Terapia por Acupuntura , Artralgia/terapia , Osteoartritis de la Rodilla/terapia , Puntos de Acupuntura , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
19.
Biomed Res Int ; 2014: 915026, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24772438

RESUMEN

Sertraline, one of the oldest antidepressants, remains to be the most efficacious treatment for depression. However, major depression disorder (MDD) is characterized by altered emotion processing and deficits in cognitive control. In cognitive interference tasks, patients with MDD have shown excessive hypothalamus activity. The purpose of this study was to examine the effects of antidepressant treatment (sertraline) on hypothalamus-anchored resting brain circuitry. Functional magnetic resonance imaging was conducted on depressed patients (n = 12) both before and after antidepressant treatment. After eight weeks of antidepressant treatment, patients with depression showed significantly increased connectivity between the hypothalamus and dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, insula, putamen, caudate, and claustrum. By contrast, decreased connectivity of the hypothalamus-related areas was primarily located in the inferior frontal gyrus, medial frontal gyrus, cingulated gyrus, precuneus, thalamus, and cerebellum. After eight weeks of antidepressant therapy, 8 out of the 12 depressed subjects achieved 70% reduction or better in depressive symptoms, as measured on the Hamilton depression rating scale. Our findings may infer that antidepressant treatment can alter the functional connectivity of the hypothalamus resting brain to achieve its therapeutic effect.


Asunto(s)
Antidepresivos/administración & dosificación , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/tratamiento farmacológico , Hipotálamo/diagnóstico por imagen , Imagen por Resonancia Magnética , Red Nerviosa/diagnóstico por imagen , Sertralina/administración & dosificación , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiografía
20.
J Mol Model ; 20(3): 2142, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24562912

RESUMEN

Inhibition of CPSF30 function by the effector domain of influenza A virus of non-structural protein 1 (NS1A) protein plays a critical role in the suppression of host key antiviral response. The CPSF30-binding site of NS1A appears to be a very attractive target for the development of new drugs against influenza A virus. In this study, structure-based molecular docking was utilized to screen more than 30,000 compounds from a Traditional Chinese Medicine (TCM) database. Four drug-like compounds were selected as potential inhibitors for the CPSF30-binding site of NS1A. Docking conformation analysis results showed that these potential inhibitors could bind to the CPSF30-binding site with strong hydrophobic interactions and weak hydrogen bonds. Molecular dynamics simulations and MM-PBSA calculations suggested that two of the inhibitors, compounds 32056 and 31674, could stably bind to the CPSF30-binding site with high binding free energy. These two compounds could be modified to achieve higher binding affinity, so that they may be used as potential leads in the development of new anti-influenza drugs.


Asunto(s)
Antivirales/química , Factor de Especificidad de Desdoblamiento y Poliadenilación/química , Medicina Tradicional China , Proteínas no Estructurales Virales/química , Algoritmos , Antivirales/metabolismo , Antivirales/farmacología , Sitios de Unión , Factor de Especificidad de Desdoblamiento y Poliadenilación/antagonistas & inhibidores , Factor de Especificidad de Desdoblamiento y Poliadenilación/metabolismo , Bases de Datos Factuales , Interacciones Huésped-Patógeno/efectos de los fármacos , Humanos , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Subtipo H1N1 del Virus de la Influenza A/metabolismo , Subtipo H1N1 del Virus de la Influenza A/fisiología , Gripe Humana/prevención & control , Gripe Humana/virología , Cinética , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Estructura Molecular , Unión Proteica/efectos de los fármacos , Estructura Terciaria de Proteína , Proteínas no Estructurales Virales/metabolismo
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