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1.
Bioconjug Chem ; 35(9): 1450-1458, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39213480

RESUMEN

A porphyrin-containing nanoscale covalent organic polymer (COP) was fabricated from 5,10,15,20-tetra(4-carboxyphenyl)porphyrin (TCPP) and cystamine via an acylation reaction. On the one hand, TCPP can induce tumor cell death by laser irradiation. Due to the presence of disulfide bonds of cystamine which can react with glutathione, it exhibits depletion of glutathione and accumulation of peroxides in tumor cells. Ultimately by the hyaluronic acid to encapsulate the COP to get S-COP@HA, the nanoparticle with a size of 168.6 nm also exhibits good tumor accumulation and biosafety. Significant inhibition of tumor cell growth was observed after two consecutive doses of S-COP@HA at relatively low laser densities. This combination therapy was proved to reduce the level of reduced glutathione in tumor cells, where ferroptosis occurs after photodynamic treatment. Overall, this study presents a potent, good therapeutic option for the effective enhancement of photodynamic therapy by glutathione depletion.


Asunto(s)
Ferroptosis , Glutatión , Fotoquimioterapia , Porfirinas , Glutatión/metabolismo , Fotoquimioterapia/métodos , Porfirinas/química , Porfirinas/farmacología , Ferroptosis/efectos de los fármacos , Humanos , Animales , Nanopartículas/química , Polímeros/química , Línea Celular Tumoral , Ratones , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Ácido Hialurónico/química
2.
Nat Chem Biol ; 17(5): 576-584, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33664521

RESUMEN

Cariogenic Streptococcus mutans is known as a predominant etiological agent of dental caries due to its exceptional capacity to form biofilms. From strains of S. mutans isolated from dental plaque, we discovered, in the present study, a polyketide/nonribosomal peptide biosynthetic gene cluster, muf, which directly correlates with a strong biofilm-forming capability. We then identified the muf-associated bioactive product, mutanofactin-697, which contains a new molecular scaffold, along with its biosynthetic logic. Further mode-of-action studies revealed that mutanofactin-697 binds to S. mutans cells and also extracellular DNA, increases bacterial hydrophobicity, and promotes bacterial adhesion and subsequent biofilm formation. Our findings provided an example of a microbial secondary metabolite promoting biofilm formation via a physicochemical approach, highlighting the importance of secondary metabolism in mediating critical processes related to the development of dental caries.


Asunto(s)
Biopelículas/efectos de los fármacos , Factores Biológicos/biosíntesis , Genes Bacterianos , Metabolismo Secundario/genética , Streptococcus mutans/metabolismo , Adhesión Bacteriana/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Factores Biológicos/aislamiento & purificación , Factores Biológicos/farmacología , Biología Computacional/métodos , ADN/genética , ADN/metabolismo , Caries Dental/microbiología , Caries Dental/patología , Regulación Bacteriana de la Expresión Génica , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Familia de Multigenes , Biosíntesis de Péptidos Independientes de Ácidos Nucleicos , Unión Proteica , Streptococcus mutans/genética , Streptococcus mutans/crecimiento & desarrollo , Streptococcus mutans/patogenicidad
3.
BMC Surg ; 19(1): 193, 2019 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-31830969

RESUMEN

BACKGROUND: Vertebral compression fracture is one of the most common complications of osteoporosis. In this study an unilateral curved vertebroplasty device was developed, and the safety, effectiveness, and surgical parameters of curved vertebroplasty (CVP) in the treatment of painful osteoporotic vertebral compression fractures was investigated and compared with traditional bipedicular vertebroplasty (BVP). METHODS: We investigated 104 vertebral augmentation procedures performed over 36 months. CVP and BVP procedures were compared for baseline clinical variables, pain relief (Visual Analog Scale, VAS), disability improvement (Oswestry Disability Index, ODI), operation time, number of fluoroscopic images, volume of cement per level, and cement leakage rate for each level treated. Complications and refracture incidence were also recorded in the two groups. RESULTS: The VAS and ODI in both group had no significant difference preoperative (P > 0.05), and a significant postoperative improvement in the VAS scores and ODI was found in both group (P < 0.001). However, the CVP group had significantly lower operation time, number of fluoroscopic images, and cement leakage rate per level than the BVP group (P < 0.05); however, the volumes of cement per level were similar in the two groups (P > 0.05). Neither group had any serious complications. Five and two patients in the BVP group developed refractures at non-adjacent and adjacent levels, respectively, with one patient developing refractures twice; however, none of the patients in the CVP group developed refractures at any level. CONCLUSIONS: Our findings revealed that both CVP and BVP were safe and effective treatments for osteoporotic vertebral compression fractures, and CVP entails a shorter operation time, less exposure to fluoroscopy, and lower rate of cement leakage.


Asunto(s)
Fracturas por Compresión/cirugía , Fracturas Osteoporóticas/cirugía , Fracturas de la Columna Vertebral/cirugía , Vertebroplastia/instrumentación , Vertebroplastia/métodos , Anciano , Cementos para Huesos , Femenino , Fluoroscopía , Fracturas por Compresión/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Dimensión del Dolor , Fracturas de la Columna Vertebral/diagnóstico por imagen , Resultado del Tratamiento , Vertebroplastia/efectos adversos , Escala Visual Analógica
4.
Pharmgenomics Pers Med ; 17: 437-442, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39319208

RESUMEN

Background: Hemiplegic migraine, a less common variant of migraine, is the focus of this paper. Within the scope of this study, we present a case of hemiplegic migraine that bears the potential for misdiagnosis, particularly as encephalitis. Brief introduction to the Disease: The patient developed a right-sided headache a day prior to admission, accompanied by fever, nausea, vomiting, and left-sided limb weakness. On the fourth day, the patient experienced a grand mal epilepsy, marked by unconsciousness, leftward deviation of both eyes, limb convulsions, and foaming at the mouth. Cerebrospinal fluid analysis revealed no apparent abnormalities, Electroencephalography showed abnormal slow waves, imaging studies indicated swelling and meningeal thickening in the right cortex, and genetic testing identified a heterozygous mutation in the ATPIA2 gene. The diagnosis was hemiplegic migraine, and the patient received symptomatic supportive treatment, leading to improvement and subsequent discharge. Flunarizine and sodium valproate were prescribed post-discharge, and the patient achieved complete recovery after a one-month follow-up. Conclusion: Apart from experiencing headaches, patients with hemiplegic migraine may exhibit additional symptoms like fever, epilepsy, and hemiplegia. These manifestations warrant clinical attention, and if deemed necessary, genetic testing should be conducted, and this is an autosomal dominant pattern.

5.
Nat Microbiol ; 9(2): 502-513, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38228859

RESUMEN

Probiotic supplements are suggested to promote human health by preventing pathogen colonization. However, the mechanistic bases for their efficacy in vivo are largely uncharacterized. Here using metabolomics and bacterial genetics, we show that the human oral probiotic Streptococcus salivarius K12 (SAL) produces salivabactin, an antibiotic that effectively inhibits pathogenic Streptococcus pyogenes (GAS) in vitro and in mice. However, prophylactic dosing with SAL enhanced GAS colonization in mice and ex vivo in human saliva. We showed that, on co-colonization, GAS responds to a SAL intercellular peptide signal that controls SAL salivabactin production. GAS produces a secreted protease, SpeB, that targets SAL-derived salivaricins and enhances GAS survival. Using this knowledge, we re-engineered probiotic SAL to prevent signal eavesdropping by GAS and potentiate SAL antimicrobials. This engineered probiotic demonstrated superior efficacy in preventing GAS colonization in vivo. Our findings show that knowledge of interspecies interactions can identify antibiotic- and probiotic-based strategies to combat infection.


Asunto(s)
Probióticos , Infecciones Estreptocócicas , Animales , Humanos , Ratones , Antibacterianos , Infecciones Estreptocócicas/microbiología , Streptococcus pyogenes , Saliva
6.
J Sep Sci ; 36(16): 2656-63, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23780651

RESUMEN

A magnetic dispersion extraction method was developed based on a molecularly imprinted magnetic microsphere (MIMM) for the selective clean-up and enrichment of tetracycline antibiotics from milk samples. The MIMMs were prepared by inverse-emulsion suspension polymerization, using doxycycline, trimethylolpropane trimethacrylate, acrylamide, methacrylic acid, and surface-modified Fe3 O4 as a template molecule, crosslinker, functional monomer, and magnetic component, respectively. Synthesis and extraction conditions were optimized for obtaining excellent affinity and high selectivity. The magnetism, covering amount, and selectivity of the magnetic microspheres were characterized by a vibrating sample magnetometer, thermogravimetric analysis, and a competitive recognition experiment. The MIMMs were applied to separate tetracycline antibiotics from milk samples by magnetic dispersion extraction, and an enrichment factor of 9.28 and a good sample clean-up were obtained. The average recoveries of four tetracycline antibiotics were obtained in the range of 74.5-93.8% with a precision of 1.2-5.2%. The LODs and LOQs of the proposed method were in the range of 7.4-19.4 and 24.7-64.7 µg/kg, respectively. The results indicated that magnetic dispersion extraction using MIMMs is a powerful tool for food-sample pretreatment with high selectivity and a simplified procedure.


Asunto(s)
Antibacterianos/aislamiento & purificación , Doxiciclina/química , Contaminación de Alimentos/análisis , Leche/química , Polímeros/química , Extracción en Fase Sólida/métodos , Tetraciclinas/aislamiento & purificación , Adsorción , Animales , Bovinos , Emulsiones/química , Magnetismo , Microesferas , Impresión Molecular , Polimerizacion , Polímeros/síntesis química , Extracción en Fase Sólida/instrumentación
7.
J Mater Sci Mater Med ; 24(8): 1985-92, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23686353

RESUMEN

This paper reports the results of an in vitro investigation into the blood response of medical grade poly (vinyl chloride) (PVC), and two types of plasticized PVC in tubing or sheet form, with di-(2-ethylhexyl)phthalate (DEHP) and di(isononyl) cyclohexane-1,2-dicarboxylate (HEXAMOLL(®) DINCH) as plasticizer, were selected for assessment of complement activation, coagulation system and platelet activation. The results of the study show that not only the plasticizers at PVC surface have an influence on complement activation, but also the incubation condition such as incubation time and the diameter of PVC tubing. Under static status, C3a, C5a and SC5b-9 concentration in the blood were higher after contacting with PVC plasticized with DEHP (PVC1) than after contacting with PVC plasticized with DINCH (PVC2). However, under dynamic circulation, the results were totally converse, which may be due to smaller diameter and higher shear rate of PVC2. In addition, there was a significant increase of activated partial thrombin time (APTT) and decrease of FIX concentration after plasma contacting with the PVC tubing, which indicated that the intrinsic pathway may be impacted when blood contacted with PVC tubing. However, there was no significant difference of APTT, FIX concentration and CD62p expression rate between the two materials. Moreover, the migration in the DINCH system was considerably lower than for DEHP, which indicates that DINCH could be a promising alterative plasticizer of DEHP.


Asunto(s)
Ensayo de Materiales , Plastificantes/farmacología , Cloruro de Polivinilo/química , Cloruro de Polivinilo/farmacología , Coagulación Sanguínea/efectos de los fármacos , Activación de Complemento/efectos de los fármacos , Complemento C3a/metabolismo , Dietilhexil Ftalato/farmacología , Humanos , Modelos Biológicos , Selectina-P/metabolismo , Activación Plaquetaria/efectos de los fármacos , Plasma Rico en Plaquetas/efectos de los fármacos , Plasma Rico en Plaquetas/metabolismo , Propiedades de Superficie/efectos de los fármacos , Humectabilidad/efectos de los fármacos
8.
Biomater Sci ; 11(23): 7655-7662, 2023 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-37850341

RESUMEN

Thromboembolism, arising from the utilization of cardiovascular medical devices, remains a prevalent issue entailing substantial morbidity and mortality. Despite the proposal of various surface modification strategies, each approach possesses inherent limitations and drawbacks. Herein, we propose a novel approach for the in situ growth of nanocoatings on various material surfaces through the cooperative assembly of silk fibroin (SF) and lysozyme. The intrinsic in situ growth characteristic enables the nanocoatings to achieve stable and uniform adherence to diverse substrate surfaces, including the inner surface of intravascular catheters, to redefine the surface properties of the material. The features of the hydrophilic and negatively charged nanocoating contribute to its antithrombotic properties, as evidenced by the reduced likelihood of platelet adhesion upon modification of the ultrathin and mechanically robust coating. In vitro assessment confirms a significant reduction in blood clot formation along with the promotion of anticoagulation. Such a SF/Ly nanocoating holds substantial promise as a surface modification strategy to enhance the hemocompatibility of medical devices and other materials that come into contact with blood, particularly in situations where medical-grade materials are temporarily unavailable, thus providing a feasible alternative.


Asunto(s)
Tromboembolia , Trombosis , Humanos , Materiales Biocompatibles Revestidos/química , Adhesividad Plaquetaria , Propiedades de Superficie
9.
Nat Commun ; 14(1): 4875, 2023 08 12.
Artículo en Inglés | MEDLINE | ID: mdl-37573353

RESUMEN

Clinical use of intraoperative auto-transfusion requires the removal of platelets and plasma proteins due to pump-based suction and water-soluble anticoagulant administration, which causes dilutional coagulopathy. Herein, we develop a carboxylated and sulfonated heparin-mimetic polymer-modified sponge with spontaneous blood adsorption and instantaneous anticoagulation. We find that intrinsic coagulation factors, especially XI, are inactivated by adsorption to the sponge surface, while inactivation of thrombin in the sponge-treated plasma effectively inhibits the common coagulation pathway. We show whole blood auto-transfusion in trauma-induced hemorrhage, benefiting from the multiple inhibitory effects of the sponge on coagulation enzymes and calcium depletion. We demonstrate that the transfusion of collected blood favors faster recovery of hemostasis compared to traditional heparinized blood in a rabbit model. Our work not only develops a safe and convenient approach for whole blood auto-transfusion, but also provides the mechanism of action of self-anticoagulant heparin-mimetic polymer-modified surfaces.


Asunto(s)
Anticoagulantes , Trastornos de la Coagulación Sanguínea , Animales , Conejos , Anticoagulantes/farmacología , Factores de Coagulación Sanguínea/metabolismo , Hemostasis , Heparina/farmacología , Hemorragia/etiología , Polímeros/farmacología
10.
Artículo en Inglés | MEDLINE | ID: mdl-22409280

RESUMEN

It is necessary to remove residual leukocytes to prevent the blood transfusion-related adverse reactions. This paper describes a facile approach for the surface modification of commercial PBT nonwoven fabrics (PBTNF), used for blood filtration, followed by immobilizing polyvinylpyrrolidone (PVP). The whole blood filtration results revealed that the five types of PBTNF-PVPs' leucocytes retention rates and erythrocyte recovery rates increased to 96% and 92% compared with the untreated PBTNF. The blood compatibilities results indicated that PVP modified PBTNFs have good blood compatibility, suggesting that PVP-modified PBTNF is a very promising blood filter for selective removal of leukocytes.


Asunto(s)
Procedimientos de Reducción del Leucocitos/instrumentación , Leucocitos/patología , Reacción a la Transfusión , Antígenos de Grupos Sanguíneos/inmunología , Eritrocitos/patología , Histocompatibilidad , Humanos , Procedimientos de Reducción del Leucocitos/métodos , Leucocitos/inmunología , Espectroscopía de Fotoelectrones , Povidona , Propiedades de Superficie
11.
Int J Nanomedicine ; 17: 1613-1632, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35411141

RESUMEN

Background: The main challenge of polymeric micelles as drug delivery systems is that the actual delivery efficiency is not as high as expected, which is closely related with the interactions with the complex biological environments such as blood components, phagocytosis, and biodistribution. Herein, we expect to understand these concerns for the clinically relevant micelles that composed of methoxypolyethylene glycol (MPEG) with identical chain length And poly(ε-caprolactone) (PCL) with tunable chain length (PCLn-MPEG) (n=20, 30, and 40) wherein doxorubicin was encapsulated as a model drug. Methods: The doxorubicin-loaded PCLn-MPEG micelles were prepared by a dialysis method and characterized by dynamic light scattering and transmission electron microscopy. The surface PEG density and chain conformation were investigated by dissipative particle dynamics simulation. The stability of the micelles was detected by nanoparticle tracking analysis. The effects of PCL chain length on the blood components, phagocytosis, and biodistribution were assayed in vitro and in vivo. Results: The micelles exhibited spherical morphology with a diameter about 30nm. The PEG chain conformation from "mushroom-like" to "brush-like" was evident. The micelles have no remarkable effect on the red blood cells, blood coagulation, and platelet activation. Interestingly, the protein adsorption was affected and dependent on the chain conformation, with lowest adsorption for PCL30-MPEG, which also has the loWest phagocytosis. The stability of the micelles was in the order of PCL40-MPEG>PCL30-MPEG>PCL20-MPEG which was dependent on the PCL chain length. The micelles mainly accumulated in liver, with the order consistent with their stability, indicating that, besides the phagocytosis, the stability of the micelle plays an important role in biodistribution as well. The related mechanisms were proposed and discussed. Conclusion: Manipulating the PEG/PCL ratio of the micelle is an effective approach to modulate the protein adsorption, phagocytosis, and biodistribution, which may be a prerequisite for clinical applications.


Asunto(s)
Sistemas de Liberación de Medicamentos , Micelas , Doxorrubicina/farmacología , Sistemas de Liberación de Medicamentos/métodos , Fagocitosis , Poliésteres , Polietilenglicoles , Distribución Tisular
12.
J Cancer Res Clin Oncol ; 148(4): 921-930, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33970299

RESUMEN

BACKGROUND: No international consensus has been reached regarding delineation of postoperative intensity-modulated radiotherapy (PO-IMRT) clinical target volumes (CTV) for major salivary gland carcinoma (SGC). The purpose of this article was to report our experience according to surgical principles. METHODS: Between June 2010 and June 2018, 54 consecutive patients were enrolled. Reserved tissues around the margin of resection that were less than 5 mm from the invasive tumour edge before surgery were defined as high-risk clinical target volumes (CTV-HD), those less than 10 mm away were defined as medium-risk CTV (CTV1), and those 10-20 mm away were defined as low-risk CTV (CTV2), and were irradiated with 63-65 Gy, 59.5-61 Gy, and 45-54 Gy, respectively. Target volume distributions of reserved tissues were analysed and actuarial estimates of overall survival (OS), recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) were obtained with the Kaplan-Meier method. RESULTS: In parotid gland tumours, the percentages of defined CTV-HD in the styloid process, mandibular ramus, posterior venter of the digastric muscle, carotid sheath and stylomastoid foramen reached 34.29%, 25.71%, 54.29%, 40.00%, and 37.10%, respectively. The median follow-up was 33 months (range, 5-98 months). The 3-year and 5-year Kaplan-Meier estimates of OS, RFS and DMFS were 85.4% and 77.8%, 97.4%, and 97.4%, and 82.0% and 82.0%, respectively. CONCLUSIONS: It is feasible to delineate CTVs according to distances between various reserved tissues and the primary tumour edge before operation.


Asunto(s)
Radioterapia de Intensidad Modulada , Neoplasias de las Glándulas Salivales , Humanos , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Neoplasias de las Glándulas Salivales/radioterapia , Neoplasias de las Glándulas Salivales/cirugía
13.
J Biomed Mater Res A ; 109(10): 1955-1966, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34085403

RESUMEN

A main problem in the design of blood-contacting biomaterials has been the deficiency of a systematic understanding of blood-biomaterial interactions and the strategy to modulate blood responses. In this work, different functional groups including carboxyl (COOH), hydroxyl (OH) and zwitterionic sulfobetaine group (⊕N((CH3 )2 )(CH2 )3 SO3-○- , SMDB) were grafted on the poly (butylene terephthalate) (PBT) film to study how the functional groups modulate blood responses and in terms of interaction with the coagulation system, the complement system, and platelets. The results showed protein absorption and platelet adhesion was stronger on the PBT bearing COOH group than PBT films bearing OH and zwitterionic sulfobetaine groups (total protein (µg/cm2 ): 32.92 ± 5.89 vs. 22.02 ± 1.44 vs. 19.09 ± 1.59; platelet adhesion (/mm2 ): 1,626.7 ± 120.1 vs. 1,395.6 ± 363.3 vs. 1,102.2 ± 373.7), which had a rougher and negatively charged surface, and the coagulation system was inhibited by binding fibrinogen (Fg) and coagulation factors. Meanwhile, PBT-PSMDB showed anticoagulant property and induced platelet activation. As a result, complement formation on these two films were less than PBT bearing OH groups by inhibiting the coagulation system (C3a (ng/ml): 3,745.4 ± 143.9 vs. 3,290.9 ± 249.7 vs. 4,887.9 ± 88.9; C5a (ng/ml): 22.1 ± 2.6 vs. 22.3 ± 1.8 vs. 27.9 ± 2.0). On the other hand, PBT bearing OH groups did not facilitate remarkable platelet adhesion and activation, and had no influence on platelet aggregation, hypotonic shock response, and coagulation system. The above results showed that the blood responses were highly interlinked, and could be modulated by grafting with different functional groups on the biomaterial surfaces. These findings may help identify a strategy to design materials with better hemocompatibility for blood contact, filtration, and purification applications.


Asunto(s)
Eritrocitos/efectos de los fármacos , Poliésteres/química , Poliésteres/farmacología , Adsorción , Coagulación Sanguínea/efectos de los fármacos , Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Plaquetas/ultraestructura , Activación de Complemento/efectos de los fármacos , Fibrinógeno/metabolismo , Hemólisis/efectos de los fármacos , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Ensayo de Materiales , Espectroscopía de Fotoelectrones , Adhesividad Plaquetaria/efectos de los fármacos , Espectroscopía Infrarroja por Transformada de Fourier , Propiedades de Superficie
14.
ACS Appl Mater Interfaces ; 13(8): 9729-9738, 2021 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-33599495

RESUMEN

Intracerebral hemorrhage (ICH) will be accompanied by the overload of iron and reactive oxygen species (ROS) following hematoma clearance. Although deferoxamine (DFO) has been widely utilized as a clinical first-line siderophore to remove the iron overload, the ROS-inducing damage still greatly limits the therapeutic effect of DFO. To address this issue, we designed and fabricated a series of dual-functional macromolecular nanoscavengers featuring high-density DFO units and catechol moieties. Note that the former units could effectively remove the iron overload, while the latter ones could efficiently deplete the ROS. The resulting nanoscavengers efficiently down-regulate the iron and ROS levels as well as significantly reduce the cell death in both iron-overloaded RAW 264.7 cells and the ICH mice model. This work suggests a novel clue for the ICH-ameliorated iron-depleting interventional therapeutic regimen.


Asunto(s)
Antioxidantes/uso terapéutico , Hemorragia Cerebral/tratamiento farmacológico , Sobrecarga de Hierro/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Polímeros/uso terapéutico , Sideróforos/uso terapéutico , Animales , Antioxidantes/síntesis química , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatología , Catecoles/síntesis química , Catecoles/uso terapéutico , Hemorragia Cerebral/inducido químicamente , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/fisiopatología , Colagenasas , Deferoxamina/análogos & derivados , Deferoxamina/uso terapéutico , Hierro/metabolismo , Sobrecarga de Hierro/etiología , Sobrecarga de Hierro/fisiopatología , Masculino , Ratones , Ratones Endogámicos BALB C , Fármacos Neuroprotectores/síntesis química , Polímeros/síntesis química , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismo , Sideróforos/síntesis química
15.
Colloids Surf B Biointerfaces ; 184: 110545, 2019 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-31629184

RESUMEN

pH-responsive nanocarriers such as polymeric micelles that self-assemble from amphiphilic copolymers containing amino groups have been limited by their significant effects on the blood and thus compromise of their hemocompatibility due to the amino group-induced positive charges. Here we report a biomimetic phosphorylcholine strategy to improve the hemocompatibility of the pH-responsive micelles with positive charges. Amphiphilic copolymers containing different number of tertiary amino groups were synthesized in five steps through ring opening polymerization, azide reaction, thio-bromo "Click" chemistry, and atom transfer radical polymerization to self-assemble biomimetic phosphorylcholine micelles with pH-responsiveness, which shown no significant effects on red blood cells, coagulation, and platelet activation. Moreover, albumin adsorption on the micelles was significantly lower than that of polycaprolactone-methoxypolyethylene glycol (PCL-mPEG) control, and in terms of immune cells, the micelles showed controllable phagocytosis that dependent on the number of tertiary amino groups, in which the one containing four tertiary amino groups in its corresponding copolymer remains had a lower phagocytosis by whole blood leukocyte than that of PCL-mPEG. Based on these results, the hemocompatibility related mechanism of the micelles was discussed and proposed. Our findings demonstrated that this biomimetic phosphorylcholine is a promising strategy to improve the hemocompatibility of the positively charged nanocarriers.


Asunto(s)
Materiales Biomiméticos/química , Fosforilcolina/química , Compuestos de Amonio Cuaternario/química , Antibióticos Antineoplásicos/química , Materiales Biomiméticos/síntesis química , Doxorrubicina/química , Liberación de Fármacos , Eritrocitos/citología , Hemólisis , Humanos , Concentración de Iones de Hidrógeno , Micelas , Estructura Molecular , Tamaño de la Partícula , Polímeros/síntesis química , Polímeros/química , Propiedades de Superficie , Tensoactivos/síntesis química , Tensoactivos/química
16.
Int J Nanomedicine ; 14: 10061-10077, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31920303

RESUMEN

PURPOSE: S-propargyl-cysteine (SPRC; alternatively known as ZYZ-802) is a novel modulator of endogenous tissue H2S concentrations with known cardioprotective and anti-inflammatory effects. However, its rapid metabolism and excretion have limited its clinical application. To overcome these issues, we have developed some novel liposomal carriers to deliver ZYZ-802 to cells and tissues and have characterized their physicochemical, morphological and pharmacological properties. METHODS: Two liposomal formulations of ZYZ-802 were prepared by thin-layer hydration and the morphological characteristics of each liposome system were assessed using a laser particle size analyzer and transmission electron microscopy. The entrapment efficiency and ZYZ-802 release profiles were determined following ultrafiltration centrifugation, dialysis tube and HPLC measurements. LC-MS/MS was used to evaluate the pharmacokinetic parameters and tissue distribution profiles of each formulation via the measurements of plasma and tissues ZYZ-802 and H2S concentrations. Using an in vivo model of heart failure (HF), the cardio-protective effects of liposomal carrier were determined by echocardiography, histopathology, Western blot and the assessment of antioxidant and myocardial fibrosis markers. RESULTS: Both liposomal formulations improved ZYZ-802 pharmacokinetics and optimized H2S concentrations in plasma and tissues. Liposomal ZYZ-802 showed enhanced cardioprotective effects in vivo. Importantly, liposomal ZYZ-802 could inhibit myocardial fibrosis via the inhibition of the TGF-ß1/Smad signaling pathway. CONCLUSION: The liposomal formulations of ZYZ-802 have enhanced pharmacokinetic and pharmacological properties in vivo. This work is the first report to describe the development of liposomal formulations to improve the sustained release of H2S within tissues.


Asunto(s)
Cisteína/análogos & derivados , Sulfuro de Hidrógeno/uso terapéutico , Miocardio/patología , Transducción de Señal , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Animales , Antioxidantes/uso terapéutico , Cardiotónicos/farmacología , Cardiotónicos/uso terapéutico , Cistationina gamma-Liasa/metabolismo , Cisteína/química , Modelos Animales de Enfermedad , Fibrosis , Insuficiencia Cardíaca/tratamiento farmacológico , Sulfuro de Hidrógeno/sangre , Liposomas , Masculino , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos
17.
Zhonghua Gan Zang Bing Za Zhi ; 16(4): 279-82, 2008 Apr.
Artículo en Zh | MEDLINE | ID: mdl-18423150

RESUMEN

OBJECTIVE: To study the responses of peginterferon-alpha 2a antiviral therapy in chronic hepatitis B (CHB) patients. METHODS: One hundred two CHB patients with their serum ALT values higher than 2x the upper limit of the normal (ULN) were divided into a HBeAg-positive and a HBeAg-negative group. All patients were treated with peginterferon-alpha 2a by subcutaneous injection (180 microgram once weekly). After treatment for 6 months, patients without a defined therapeutic response were dropped from the treatment group; the others completed a 12 month therapy. The sustained response and the antiviral effect of the treatment were assessed at the end of the therapy. To investigate the possible impact factors of the response to peginterferon-alpha 2a, we studied the therapeutic response of patients with different serum ALT levels, inflammation grades of liver histology, stages of fibrosis, and HBV viral load levels. RESULTS: (1) There was no statistical difference of the rates of response at the end of treatment and 6, 12, 18, 24 and 30 months after the cessation of therapy between the HBeAg-positive and the HBeAg-negative groups. (2) In the HBeAg-positive group, the rates of response of patients with serum ALT values>3*ULN were significantly higher than those with serum ALT values less than 3*ULN (x2=4.40). However, no statistical difference of serum ALT levels was found in the HBeAg-negative group. (3) In both HBeAg-positive and HBeAg-negative groups, no difference was revealed in the rates of response among patients with different levels of HBV viral loads. (4) In the HBeAg-positive group, patients with more severe liver inflammation histologically (G3 and G4) had significantly higher response rates than those with milder inflammation (G1 and G2) (x2=4.19), but no similar statistical differences were found in the HBeAg-negative group. Moreover, there was no difference in the rates of response among patients in different stages of liver fibrosis in both HBeAg-positive and HBeAg-negative groups. CONCLUSIONS: Similar rates of response and sustained virological response to the peginterferon-alpha 2a treatment can be achieved in both HBeAg-positive and HBeAg-negative patients. Hepatic fibrosis is not a predictor of poor therapeutic response. For HBeAg-positive patients, more severe liver inflammation identified with liver biopsies (G3 or G4) and high serum ALT values (more than 3*ULN) can be considered as predictors of a good therapeutic response.


Asunto(s)
Antivirales/uso terapéutico , Hepatitis B Crónica/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Polietilenglicoles/uso terapéutico , Adolescente , Adulto , Femenino , Hepatitis B Crónica/patología , Humanos , Interferón alfa-2 , Hígado/patología , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , Adulto Joven
18.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 25(1): 131-4, 2008 Feb.
Artículo en Zh | MEDLINE | ID: mdl-18435274

RESUMEN

The evaluation of the adsorption of methylene blue (MB) in water by the sulfonated polyethersulfone (SPES) adsorbent column was carried out in this study after the SPES was prepared by gassy SO3 method. The polyethersulfone (PES) adsorbent column was used as control. The results indicated that the adsorption of MB by adsorbent column of SPES was more efficient than that of PES. In addition, the effect of the flow rate or ionic intensity on the adsorption and desorption of MB in water by SPES adsorbent column were also investigated. The results showed that the removal rate in water by SPES adsorbent column was larger than that in saline. However, the desorption experiment revealed that the desorption amount of the SPES adsorbent column in saline was larger than that in water.


Asunto(s)
Azul de Metileno/aislamiento & purificación , Polímeros/química , Polímeros/síntesis química , Sulfonas/química , Sulfonas/síntesis química , Agua/química , Adsorción , Soluciones
19.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 25(1): 135-8, 2008 Feb.
Artículo en Zh | MEDLINE | ID: mdl-18435275

RESUMEN

The evaluation of the adsorption of methylene blue (MB) in plasma by sulfonated polyethersulfone (SPES) adsorbent column was carried out in this study. The results indicated the adsorption of MB by SPES adsorbent column was more efficient than that by polyethersulfone (PES). In addition, the changes of the concentration of BSA solution passing through adsorbent column along with the time and the biochemical indices of plasma before and after adsorption treatment were also investigated. The results showed that the adsorption amount of BSA by PES adsorbent column was larger than that by SPES, and the biochemical parameters such as total protein, albumin, glucose, triglyceride and total cholesterol in plasma varied slightly before and after passing through the column, which were still within the clinical indices.


Asunto(s)
Azul de Metileno/aislamiento & purificación , Plasma/química , Polímeros/química , Polímeros/síntesis química , Sulfonas/química , Sulfonas/síntesis química , Adsorción , Humanos , Albúmina Sérica Bovina/química
20.
J Orthop Surg Res ; 10: 33, 2015 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-25879225

RESUMEN

BACKGROUND: Anterior C2/3 discectomy and interbody fusion (ACDF) with plating is increasingly performed as the primary treatment of unstable Hangman's fracture; however, plate-related complications, such as screw back-out, plate fracture and soft-tissue injury, is not uncommon. Polyetheretherketone (PEEK) cage has now been developed to provide initial stability before fusion; however, whether and how ACDF with PEEK cage offer better clinical results compared with ACDF with plating in management of Hangman's fracture remains unknown. This study compares the efficacy of ACDF with plating to that of ACDF with PEEK cage in management of type II/IIA Hangman's fractures (according to Levine and Edwards classification) retrospectively. METHODS: From February 2006 to March 2012, a total of 21 patients with type II/IIA Hangman's fractures combined with intervertebral disc injury underwent ACDF with PEEK cage, and 28 patients underwent ACDF with plating. Perioperative parameters were compared. The average follow-up period was 50.3 months (range 27-76 months). The clinical outcome (visual analog scale (VAS), American Spinal Injury Association (ASIA) scale, and clinical post-traumatic neck score (PTNC)) and radiological outcome (translation of C2, local kyphotic angle (LKA), and fusion status of C2/3) was compared retrospectively. RESULTS: The operative time and blood loss were significantly less in the ACDF with cage group compared with that in the ACDF with plating group (P < 0.05). All patients showed neurological recovery and achieved solid fusion. There were no significant differences in the clinical and radiological outcomes at final follow-up between groups, except in the LKA and the correction loss rate of LKA which were higher in the ACDF with plating group (P < 0.05). Donor-site pain occurred in two patients (10.1%) within 6 months after operation in the ACDF with plating group and none in the ACDF with cage group. All patients recovered without any adverse effects. CONCLUSIONS: ACDF with PEEK cage is effective and reliable in management of type II/IIA Hangman's fractures and is more cost-effective due to shorter operative time and less blood loss requirements.


Asunto(s)
Vértebra Cervical Axis/lesiones , Trasplante Óseo , Fijación Interna de Fracturas/métodos , Fijadores Internos , Fracturas de la Columna Vertebral/cirugía , Adulto , Vértebra Cervical Axis/diagnóstico por imagen , Benzofenonas , Femenino , Fijación Interna de Fracturas/efectos adversos , Fijación Interna de Fracturas/instrumentación , Humanos , Disco Intervertebral/lesiones , Cetonas , Masculino , Persona de Mediana Edad , Polietilenglicoles , Polímeros , Radiografía , Estudios Retrospectivos , Fracturas de la Columna Vertebral/diagnóstico por imagen , Trasplante Autólogo , Resultado del Tratamiento , Vertebroplastia
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