Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 25
Filtrar
Más filtros

Bases de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
J Phys Ther Sci ; 34(4): 269-274, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35400834

RESUMEN

[Purpose] This study aimed to elucidate the effects of upper extremity loading on pelvic movements during wheeled upright walker use. [Participants and Methods] Thirteen healthy male adults participated in this intervention study. Participants walked under five conditions with targeted loads on their upper extremities of 0%, 10%, 20%, 30%, and 40% of their body weights using a wheeled upright walker with armrests. Measured items included gait velocity and stride length; the angle of the maximum trunk anterior tilt; the range of motion of the trunk and pelvis in the movements of obliquity, tilt, and rotation; and the amplitude of the center of mass in the vertical and lateral directions captured and calculated using a three-dimensional motion analysis system. [Results] Increasing the load on the upper extremities did not shorten the stride or restrict pelvic movement during gait using upright walker use. The range of pelvic rotation with walker use increased versus that of the standard gait. [Conclusion] The pelvis showed quantitative movements during gait using the wheeled upright walker with armrests. These results could be helpful in the development of robotic assistive devices.

2.
Metab Eng ; 65: 178-184, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33246165

RESUMEN

Terpenoids are a class of natural compounds with many important functions and applications. They are synthesized from a long synthetic pathway of isoprenyl unit coupling with the myriads of terpene synthases. Owing to the catalytic divergence of terpenoids synthesis, microbial production of terpenoids is compromised to the complexity of pathway engineering and suffers from the metabolic engineering burden. In this work, the adaptive Escherichia coli HP variant exhibited a general cell fitness in terpenoid synthesis. Especially, it could yield taxadiene of 193.2 mg/L in a test tube culture, which is a five-fold increase over the production in the wild type E. coli DH5α. Mutational analyses indicated that IS10 insertion in adenylate cyclase CyaA (CyaAHP) resulted in lowering intracellular cyclic AMP (cAMP), which could regulate its receptor protein CRP to rewire cell metabolism and contributed to the improved cell fitness. Our results suggested a way to manipulate cell fitness for terpenoids production and other products.


Asunto(s)
AMP Cíclico , Escherichia coli , Terpenos , Escherichia coli/genética , Ingeniería Metabólica
3.
Microb Cell Fact ; 18(1): 55, 2019 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-30885243

RESUMEN

Naturally occurring carotenoids have been isolated and used as colorants, antioxidants, nutrients, etc. in many fields. There is an ever-growing demand for carotenoids production. To comfort this, microbial production of carotenoids is an attractive alternative to current extraction from natural sources. This review summarizes the biosynthetic pathway of carotenoids and progresses in metabolic engineering of various microorganisms for carotenoid production. The advances in synthetic pathway and systems biology lead to many versatile engineering tools available to manipulate microorganisms. In this context, challenges and possible directions are also discussed to provide an insight of microbial engineering for improved production of carotenoids in the future.


Asunto(s)
Fenómenos Fisiológicos Bacterianos , Carotenoides/biosíntesis , Carotenoides/genética , Ingeniería Metabólica/métodos , Microorganismos Modificados Genéticamente/química
4.
Molecules ; 22(2)2017 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-28178225

RESUMEN

Emodin is a component in a Chinese herb, Rheum officinale Baill, traditionally used for diabetes and anticancer. Its poor solubility is one of the major challenges to pharmaceutical scientists. We previously reported on thermoreversible gel formulations based on poloxamer for the topical delivery of emodin. The present study was to understand the effect of poloxamer type on emodin solubility and its application in cellular activity screening. Various gel formulations composed of poloxamer 407 (P407), poloxamer 188 (P188) and PEG400 were prepared and evaluated. Major evaluation parameters were the gelation temperature (Tgel) and solubility of emodin. The emodin solubility increased with increasing poloxamer concentration and the Tgel was modulated by the proper combination of P407. In particular, this study showed that the amount of P407 in thermoreversible poloxamer gel (PG) was the dominant factor in enhancing solubility and P188 was effective at fixing gelation temperature in the desired range. A thermoreversible emodin PG was selected as the proper composition with the liquid state at room temperature and gel state at body temperature. The gel showed the solubility enhancement of emodin at least 100-fold compared to 10% ethanol or water. The thermoreversible formulation was applied for in vitro cellular activity screening in the human dermal fibroblast cell line and DLD-1 colon cancer cell line after dilution with cell culture media. The thermoreversible gel formulation remained as a clear solution in the microplate, which allowed reliable cellular activity screening. In contrast, emodin solution in ethanol or DMSO showed precipitation at the corresponding emodin concentration, complicating data interpretation. In conclusion, the gel formulation is proposed as a useful prototype topical formulation for testing emodin in vivo as well as in vitro.


Asunto(s)
Emodina/química , Poloxámero/química , Administración Tópica , Línea Celular Tumoral , Forma de la Célula/efectos de los fármacos , Química Farmacéutica , Evaluación Preclínica de Medicamentos , Emodina/farmacología , Fibroblastos/efectos de los fármacos , Fibroblastos/fisiología , Geles , Humanos , Solubilidad , Solventes/química
5.
Clin Immunol ; 148(2): 219-26, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23778261

RESUMEN

The efficient development of tolerance-inducing therapies and safe reduction of immunosuppression should be supported by early diagnosis and prediction of tolerance in transplantation. Using mouse models of donor-specific tolerance to allogeneic skin and islet grafts we tested whether measurement of tolerance-related gene expression in their alloantigen-reactive peripheral T cell fraction efficiently reflected the tolerance status of recipients. We found that Foxp3, Nrn1, and Klrg1 were preferentially expressed in conditions of tolerance compared with rejection or unmanipulated controls if their expression is measured in CD69(+) T cells prepared from coculture of recipient peripheral T cells and donor antigen-presenting cells. The same pattern of gene expression was observed in recipients grafted with either skin or islets, recipients of different genetic origins, and even those taking immunosuppressive drugs. These findings suggest that the expression of tolerance-related genes in the alloantigen-reactive T cell fraction could be used to detect tolerance in the clinic.


Asunto(s)
Regulación de la Expresión Génica/inmunología , Tolerancia Inmunológica/fisiología , Isoantígenos/inmunología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Animales , Técnicas de Cocultivo , Ciclosporina/farmacología , Tolerancia Inmunológica/inmunología , Inmunosupresores/farmacología , Trasplante de Islotes Pancreáticos/inmunología , Ratones , Ratones Endogámicos , Sirolimus/farmacología , Trasplante de Piel/inmunología , Organismos Libres de Patógenos Específicos , Bazo/citología
6.
Biomolecules ; 13(2)2023 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-36830587

RESUMEN

BACKGROUND: Activated Cdc42-associated kinase (ACK1) is essential for numerous cellular functions, such as growth, proliferation, and migration. ACK1 signaling occurs through multiple receptor tyrosine kinases; therefore, its inhibition can provide effective antiproliferative effects against multiple human cancers. A number of ACK1-specific inhibitors were designed and discovered in the previous decade, but none have reached the clinic. Potent and selective ACK1 inhibitors are urgently needed. METHODS: In the present investigation, the pharmacophore model (PM) was rationally built utilizing two distinct inhibitors coupled with ACK1 crystal structures. The generated PM was utilized to screen the drug-like database generated from the four chemical databases. The binding mode of pharmacophore-mapped compounds was predicted using a molecular docking (MD) study. The selected hit-protein complexes from MD were studied under all-atom molecular dynamics simulations (MDS) for 500 ns. The obtained trajectories were ranked using binding free energy calculations (ΔG kJ/mol) and Gibb's free energy landscape. RESULTS: Our results indicate that the three hit compounds displayed higher binding affinity toward ACK1 when compared with the known multi-kinase inhibitor dasatinib. The inter-molecular interactions of Hit1 and Hit3 reveal that compounds form desirable hydrogen bond interactions with gatekeeper T205, hinge region A208, and DFG motif D270. As a result, we anticipate that the proposed scaffolds might help in the design of promising selective ACK1 inhibitors.


Asunto(s)
Antineoplásicos , Proteínas Tirosina Quinasas , Humanos , Proteínas Tirosina Quinasas/metabolismo , Simulación del Acoplamiento Molecular , Transducción de Señal , Dasatinib
7.
J Clin Med ; 11(1)2022 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-35012001

RESUMEN

BACKGROUND: nosocomial sepsis remains a significant source of morbidity and mortality in extremely low birth weight (ELBW) infants. Early and accurate diagnosis is very important, but it is difficult due to the similarities in clinical manifestation between the causative microorganisms. We tried to identify the differences between causative microorganisms in clinical and laboratory findings and to help choose antibiotics, when sepsis was suspected in ELBW infants. METHODS: a retrospective study was conducted on preterm infants, born at less than 28 weeks of gestation, with a birth weight of less than 1000 g between January 2009 and December 2019. Clinical and laboratory findings of suspected sepsis, after the first 72 h of life, were assessed. We classified them into four groups according to blood culture results (gram positive, gram negative, fungal, and negative culture groups) and compared them. RESULTS: a total of 158 patients were included after using the exclusion criteria, with 45 (29%) in the gram positive group, 35 (22%) in the gram negative group, 27 (17%) in the fungal group, and 51 (32%) in the negative culture group. There were no significant differences in mean gestational age, birth weight, and neonatal morbidities, except for the age of onset, which was earlier in the fungal group than other groups. White blood cell (WBC) counts were the highest in the gram negative group and the lowest in the fungal group. The mean platelet counts were the lowest in the fungal group. C-reactive protein (CRP) levels were the highest in the gram negative group, while glucose was the highest in the fungal group. CONCLUSIONS: in conclusion, we showed that there are some differences in laboratory findings, according to causative microorganisms in the nosocomial sepsis of ELBW infants. Increased WBC and CRP were associated with gram negative infection, while decreased platelet and glucose level were associated with fungal infection. These data may be helpful for choosing empirical antibiotics when sepsis is suspected.

8.
J Clin Med ; 11(13)2022 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-35806993

RESUMEN

BACKGROUND: The etiology of small for gestational age (SGA) is multifactorial and includes maternal/uterine-placental factors, fetal epigenetics, and genetic abnormalities. We evaluated the genetic causes and diagnostic effectiveness of targeted-panel sequencing (TES) or whole-exome sequencing (WES) in SGA infants without a known cause. METHODS: A prospective study was conducted on newborn infants born with a birth weight of less than the 10th percentile for gestational age between January 2019 and December 2020 at the Pusan National University Hospital. We excluded infants with known causes of SGA, including maternal causes or major congenital anomalies or infections. SGA infants without a known etiology underwent genetic evaluation, including karyotyping, chromosomal microarray (CMA), and TES/WES. RESULTS: During the study period, 82 SGA infants were born at our hospital. Among them, 61 patients were excluded. A total of 21 patients underwent karyotyping and chromosomal CMA, and aberrations were detected in two patients, including one chromosomal anomaly and one copy number variation. Nineteen patients with normal karyotype and CMA findings underwent TES or WES, which identified three pathogenic or likely pathogenic single-gene mutations, namely LHX3, TLK2, and MED13L. CONCLUSIONS: In SGA infants without known risk factors, the prevalence of genetic causes was 22% (5/21). The diagnostic yield of TES or WES in SGA infants with normal karyotype and CMA was 15.7% (3/19). TES or WES was quite helpful in identifying the etiology in SGA infants without a known cause.

9.
Cytotherapy ; 13(1): 19-29, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21142900

RESUMEN

BACKGROUND AIMS: Recent evidence has suggested that transplanted bone marrow (BM)-derived mesenchymal stromal cells (MSC) are able to engraft and repair non-hematopoietic tissues successfully, including central nervous system, renal, pulmonary and skin tissue, and may possibly contribute to tissue regeneration. We examined the cytoprotective effect of BM MSC on co-cultured, isolated pancreatic islets. METHODS: Pancreatic islets and MSC isolated from Lewis rats were divided into four experimental groups: (a) islets cultured alone (islet control); (b) islets cultured in direct contact with MSC (IM-C); (c) islets co-cultured with MSC in a Transwell system, which allows indirect cell contact through diffusible media components (IM-I); and (d) MSC cultured alone (MSC control). The survival and function of islets were measured morphologically and by analyzing insulin secretion in response to glucose challenge. Cytokine profiles were determined using a cytokine array and enzyme-linked immunosorbent assays. RESULTS: Islets contact-cultured with MSC (IM-C) showed sustained survival and retention of glucose-induced insulin secretory function. In addition, the levels of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) were decreased, and tissue inhibitor of metalloproteinases-1 (TIMP-1) and vascular endothelial growth factor (VEGF) levels were increased at 4 weeks in both the IM-C and IM-I groups. CONCLUSIONS: These results indicate that contact co-culture is a major factor that contributes to islet survival, maintenance of cell morphology and insulin function. There might also be a synergic effect resulting from the regulation of inflammatory cytokine production. We propose that BM MSC are suitable for generating a microenvironment favorable for the repair and longevity of pancreatic islets.


Asunto(s)
Células de la Médula Ósea/citología , Insulina/metabolismo , Islotes Pancreáticos/citología , Islotes Pancreáticos/metabolismo , Células Madre Mesenquimatosas/citología , Animales , Adhesión Celular , Forma de la Célula , Supervivencia Celular , Técnicas de Cocultivo , Citocinas/metabolismo , Glucagón/metabolismo , Mediadores de Inflamación/metabolismo , Secreción de Insulina , Células Madre Mesenquimatosas/metabolismo , Fenotipo , Ratas , Ratas Endogámicas Lew , Células del Estroma/citología
10.
J Agric Food Chem ; 69(44): 13135-13142, 2021 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-34709805

RESUMEN

α-Santalene belongs to a class of natural compounds with many physiological functions and medical applications. Advances in metabolic engineering enable non-native hosts (e.g., Escherichia coli) to produce α-santalene, the precursor of sandalwood oil. However, imbalances in enzymatic activity often result in a metabolic burden on hosts and repress the synthetic capacity of the desired product. In this work, we manipulated ribosome binding sites (RBSs) to optimize an α-santalene synthetic operon in E. coli, and the best engineered E. coli NA-IS3D strain could produce α-santalene at a titer of 412 mg·L-1. Concerning the observation of the inverse correlation between indole synthesis and α-santalene production, this study speculated that indole-associated amino acid metabolism would be competitive to the synthesis of α-santalene rather than indole toxicity itself. The deletion of tnaA could lead to a 1.5-fold increase in α-santalene production to a titer of 599 mg·L-1 in E. coli tnaA- NA-IS3D. Our results suggested that the optimization of RBS sets of the synthetic module and attenuation of the competitive pathway are promising approaches for improving the production of terpenoids including α-santalene.


Asunto(s)
Escherichia coli , Ingeniería Metabólica , Escherichia coli/genética , Aceites de Plantas , Sesquiterpenos Policíclicos , Sesquiterpenos
11.
Pharmaceutics ; 12(4)2020 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-32276508

RESUMEN

Topical imageplication of epidermal growth fctor (EGF) has been used to accelerate diabetic foot ulcers but with limited efficacy. In this study, we selected a complex coacervate (EGF-Coa) composed of the low molecular weight gelatin type A and sodium alginate as a novel delivery system for EGF, based on encapsulation efficiency and protection of EGF from protease. EGF-Coa enhanced in vitro migration of keratinocytes and accelerated wound healing in streptozotocin-induced diabetic mice with increased granulation and re-epithelialization. While diabetic wound sites without treatment showed downward growth of hyperproliferative epidermis along the wound edges with poor matrix formation, EGF-Coa treatment recovered horizontal migration of epidermis over the newly deposited dermal matrix. EGF-Coa treatment also resulted in reduced levels of proinflammatory cytokines IL-1, IL-6, and THF-α. Freeze-dried coacervates packaged in aluminum pouches were stable for up to 4 months at 4 and 25 °C in terms of appearance, purity by RP-HPLC, and in vitro release profiles. There were significant physical and chemical changes in relative humidity above 33% or at 37 °C, suggesting the requirement for moisture-proof packaging and cold chain storage for long term stability. We propose low molecular weight gelatin type A and sodium alginate (LWGA-SA) coacervates as a novel EGF delivery system with enhanced efficacy for chronic wounds.

12.
Biomed Pharmacother ; 121: 109613, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31707336

RESUMEN

Diabetic foot ulcers represent one of the major and rising health issues, as the number of diabetic patients is increasing. MicroRNAs (miRNAs) are among various bioactive molecules under investigation for diabetic wound healing. The prolonged pro-inflammatory phase in diabetic wounds partly attributes to its non-healing nature. Therefore, we hypothesized that miRNA-497, known for its regulation of inflammatory responses, would enhance diabetic wound healing. We screened miRNA candidates, including miRNA-497 in the wounded skin of streptozotocin-induced type 1 diabetic mice. The therapeutic potential of miRNA-497 mimic was studied by intradermal injection around the wound in diabetic mice. In addition, the effects of miRNA-497 on pro-inflammatory cytokines were analyzed in the wound lesion of diabetic mice, and in human dermal fibroblasts cells exposed to high glucose and lipopolysaccharide.We found a significant reduction of miRNA-497 expression in the dermal wounds of the diabetic mice relative to normal mice. Intradermal injection of miRNA-497 around the full-thickness dermal wounds in diabetic mice accelerated wound closure effectively compared to the control miRNA. miRNA-497 treatment in vivo and in vitro decreased representative pro-inflammatory cytokines such as IL-1ß, IL-6, and TNF-α. Such anti-inflammatory effects of miRNA-497 shed light on its role in accelerating diabetic wound healing. In conclusion, miRNA-497, with its down-regulation activity for pro-inflammatory cytokines, is proposed as a potential therapeutic agent for diabetic wound healing.


Asunto(s)
Antiinflamatorios/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , MicroARNs/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Células Cultivadas , Citocinas/genética , Diabetes Mellitus Experimental/fisiopatología , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , MicroARNs/análisis , MicroARNs/fisiología , Estreptozocina , Cicatrización de Heridas/fisiología
13.
Pharmaceutics ; 11(10)2019 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-31614977

RESUMEN

Gelatin Type A (GA) and sodium alginate (SA) complexes were explored to encapsulate epidermal growth factor (EGF), and thereby to circumvent its proteolytic degradation upon topical application to chronic wounds. Phase diagrams were constructed based on turbidity as a function of GA to SA ratio and pH. Various GA-SA mixtures were compared for polydispersity index, zeta potential, Z-average, and ATR-FTIR spectra. Trypsin digestion and human dermal fibroblast scratch wound assay were done to evaluate the effects of EGF encapsulation. The onset pH values for coacervation and precipitation were closer together in high molecular weight GA (HWGA)-SA reaction mixtures than in low molecular weight GA (LWGA)-SA, which was attributed to strong H-bonding interactions between HWGA and SA probed by ATR-FTIR. EGF incorporation in both HWGA-SA precipitates and LWGA-SA coacervates below the isoelectric point of EGF, but not above it, suggests the contribution of electrostatic interactions between EGF and SA. EGF encapsulated in LWGA-SA coacervates was effectively protected from trypsin digestion and showed better in vitro scratch wound activity compared to free EGF. LWGA-SA coacervates are suggested as a novel delivery system for topical application of EGF to chronic wounds.

14.
J Clin Hypertens (Greenwich) ; 10(3): 176-84, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18326962

RESUMEN

Many Korean American persons have hypertension, but competing life priorities often prevent them from attending health-promotion educational activities. Using principles of community-based participatory research, the authors conducted a prospective clinical trial to determine the effectiveness of a mailed vs an in-class culturally tailored education intervention. A total of 380 hypertensive Korean American persons from the Baltimore/Washington area were assigned to a more intense in-class education group or a less intensive mail education group. Evaluation of postintervention blood pressure (BP) outcomes revealed that significant reductions in systolic BP (13.3 mm Hg and 16.1 mm Hg, respectively) and diastolic BP (9.5 mm Hg and 10.9 mm Hg) and increases in BP control rates (42.3% and 54.3%) were achieved in both groups. No significant differences in BP outcomes between groups, however, were found. In conclusion, education by mail was an effective strategy for improving BP control and may be a viable approach for other immigrant groups if the education materials address their cultural needs.


Asunto(s)
Asiático/educación , Servicios de Salud Comunitaria , Emigrantes e Inmigrantes , Hipertensión/etnología , Educación del Paciente como Asunto/métodos , Servicios Postales , Autocuidado/métodos , Adulto , Baltimore , Monitoreo Ambulatorio de la Presión Arterial , Terapia Cognitivo-Conductual , Consejo , District of Columbia , Femenino , Estudios de Seguimiento , Conductas Relacionadas con la Salud/etnología , Humanos , Hipertensión/terapia , Masculino , Persona de Mediana Edad , Multilingüismo , Estudios Prospectivos , Teléfono
15.
Int J Biol Macromol ; 117: 427-434, 2018 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-29775708

RESUMEN

Complex coacervates based on natural biopolymers have been explored as a protein delivery system to provide controlled release of loaded protein and circumvent the proteolytic degradation in chronic wounds. The coacervates composed of gelatin A (GA) and sodium alginate (SA) were optimized with respect to turbidity, size, zeta potential, and polydispersity index. Bovine serum albumin (BSA), a model protein, was effectively encapsulated in the coacervates, resulting in protection from trypsin digestion and controlled release. In contrast, EGF was not encapsulated in the same coacervates. Striking difference in the encapsulation efficiencies of BSA and EGF, despite their similar net charges, was attributed to their different levels of binding to GA based on the surface plasmon resonance (SPR) biosensor analysis. In conclusion, GA and SA coacervates can protect the encapsulated protein from proteolytic degradation, demonstrating its potential as a delivery system in the chronic wounds. SPR biosensor is proposed as an analytical tool to study the interactions between polymers and proteins in association with encapsulation efficiency in complex coacervation. The results of EGF studies suggested that GA was not a suitable polymer for EGF encapsulation and therefore, further investigation would be needed to find suitable polymer systems for improved encapsulation efficiency.


Asunto(s)
Alginatos/química , Gelatina/química , Proteolisis , Resonancia por Plasmón de Superficie/métodos , Animales , Bovinos , Factor de Crecimiento Epidérmico/química , Liofilización , Ácido Glucurónico/química , Ácidos Hexurónicos/química , Concentración de Iones de Hidrógeno , Cinética , Albúmina Sérica Bovina/química
16.
Eur J Pharm Sci ; 112: 102-111, 2018 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-29133242

RESUMEN

Release test methods for topical dosage forms including pharmacopeial tests require a large volume of release media, with limited application for high throughput screening. In the present study, we evaluated Transwell assay to miniaturize the release test method for optimization of thermoreversible topical gel formulations. We also explored the osmotic effect on the in vitro release rates from gel formulations to understand the bio-relevance of release media. An extreme vertices type of mixture design in Minitab®16 generated eleven formulations composed of poloxamer 407, poloxamer 188, and phosphate buffered saline (PBS). A quadratic equation adequately described the composition dependence of gelation temperature. Epidermal growth factor (EGF) and trypan blue were used as model drugs for proteins and small molecules, respectively. Cumulative release in PBS containing 30% sucrose exhibited linear correlation with respect to the gel compositions, while PBS without sucrose did not differentiate various compositions. Higher release rates in PBS than in sucrose media are attributable to the osmotic water flow from PBS into the donor phase, and subsequent increase in diffusivity. The time course of in vivo near-infrared fluorescence imaging of topical EGF gels on the wound sites were consistent with the in vitro release profiles measured with PBS as the release media. To the best of our knowledge, this is the first study to propose a release test method suitable for high throughput screening of topical formulations with emphasis on the osmotic pressure effect. Bio-relevant release media composition for a topical formulation would vary depending on its clinical application because the osmotic water flow through the normal skin would be negligible compared to compromised skin.


Asunto(s)
Química Farmacéutica/métodos , Liberación de Fármacos , Geles , Presión Osmótica , Administración Tópica , Animales , Factor de Crecimiento Epidérmico/administración & dosificación , Factor de Crecimiento Epidérmico/química , Masculino , Ratones Endogámicos BALB C , Poloxámero/química , Cloruro de Sodio/química , Azul de Tripano/química
17.
Front Microbiol ; 9: 2460, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30369922

RESUMEN

Terpenoids, also called isoprenoids, are a large and highly diverse family of natural products with important medical and industrial properties. However, a limited production of terpenoids from natural resources constrains their use of either bulk commodity products or high valuable products. Microbial production of terpenoids from Escherichia coli and yeasts provides a promising alternative owing to available genetic tools in pathway engineering and genome editing, and a comprehensive understanding of their metabolisms. This review summarizes recent progresses in engineering of industrial model strains, E. coli and yeasts, for terpenoids production. With advances of synthetic biology and systems biology, both strains are expected to present the great potential as a platform of terpenoid synthesis.

18.
Biotechnol Biofuels ; 11: 210, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30061932

RESUMEN

BACKGROUND: Current petroleum-derived fuels such as gasoline (C5-C12) and diesel (C15-C22) are complex mixtures of hydrocarbons with different chain lengths and chemical structures. Isoprenoids are hydrocarbon-based compounds with different carbon chain lengths and diverse chemical structures, similar to petroleum. Thus, isoprenoid alcohols such as isopentenol (C5), geraniol (C10), and farnesol (C15) have been considered to be ideal biofuel candidates. NudB, a native phosphatase of Escherichia coli, is reported to dephosphorylate isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) into isopentenol. However, no attention has been paid to its promiscuous activity toward longer chain length (C10-C15) prenyl diphosphates. RESULTS: In this study, the promiscuous activity of NudB toward geranyl diphosphate (GPP) and farnesyl diphosphate (FPP) was applied for the production of isoprenoid alcohol mixtures, including isopentenol, geraniol, and farnesol, and their derivatives. E. coli was engineered to produce a mixture of C5 and C15 alcohols by overexpressing NudB (dihydroneopterin triphosphate diphosphohydrolase) and IspA (FPP synthase) along with a heterologous MVA pathway, which resulted in a total of up to 1652 mg/L mixture of C5 and C15 alcohols and their derivatives. The production was further increased to 2027 mg/L by overexpression of another endogenous phosphatase, AphA, in addition to NudB. Production of DMAPP- and FPP-derived alcohols and their derivatives was significantly increased with an increase in the gene dosage of idi, encoding IPP isomerase (IDI), indicating a potential modulation of the composition of the alcohols mixture according to the expression level of IDI. When IspA was replaced with its mutant IspA*, generating GPP in the production strain, a total of 1418 mg/L of the isoprenoid mixture was obtained containing C10 alcohols as a main component. CONCLUSIONS: The promiscuous activity of NudB was newly identified and successfully used for production of isoprenoid-based alcohol mixtures, which are suitable as next-generation biofuels or commodity chemicals. This is the first successful report on high-titer production of an isoprenoid alcohol-based mixture. The engineering approaches can provide a valuable platform for production of other isoprenoid mixtures via a proportional modulation of IPP, DMAPP, GPP, and FPP syntheses.

19.
J Cardiovasc Nurs ; 22(5): 397-404, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17724422

RESUMEN

AIM: To examine predictors of intentional and unintentional nonadherence to antihypertensive medication regimens and their relationships to blood pressure outcomes. BACKGROUND: Although poor adherence to medical regimens is a major concern in the care of patients with high blood pressure (HBP), our understanding of the complex behavior related to adherence is limited. Moreover, few studies have been devoted to understanding adherence issues in ethnic minority groups, such as the interplay between cultural beliefs and HBP medication-taking behaviors. DESIGN: A cross-sectional analysis was performed to assess the factors affecting nonadherence to antihypertensive medication regimens. METHODS: The data used in this analysis came from an ongoing HBP intervention trial involving middle-aged (40-64 years) Korean Americans with HBP. A total of 445 Korean Americans with HBP was enrolled in the trial at baseline. Of these, 208 participants who were on antihypertensive medication were included in the analysis. Using multivariate logistic regression, we examined theoretically selected variables to assess their relationships to intentional and unintentional nonadherence in this sample. RESULTS: Approximately 53.8% of the subjects endorsed 1 or more types of nonadherent behaviors. After controlling for demographic variables, multivariate analysis revealed that a greater number of side effects from the medication (adjusted odds ratio [OR], 1.19; 95% confidence interval [CI], 1.07 to 1.33) and a lower level of HBP knowledge (adjusted OR, 0.89; 95% CI, 0.79 to 0.99) were significantly associated with intentional nonadherence. Unintentional nonadherence was less strongly associated with the study variables examined in the analysis. CONCLUSION: Our findings indicate that intentional nonadherence to antihypertensive medication that stems from incomplete knowledge of HBP treatment is prevalent among middle-aged Korean Americans with HBP. The results highlight the strong need for an intervention that focuses on increasing patient knowledge about HBP, including the benefits and side effects of antihypertensive medication. This type of focused intervention may help reduce intentional nonadherence to antihypertensive medications and ultimately result in achieving adequate BP control in this high-risk group.


Asunto(s)
Antihipertensivos/uso terapéutico , Asiático/estadística & datos numéricos , Conocimientos, Actitudes y Práctica en Salud , Hipertensión/tratamiento farmacológico , Hipertensión/etnología , Negativa del Paciente al Tratamiento/etnología , Adulto , Baltimore/epidemiología , Estudios Transversales , Toma de Decisiones , District of Columbia/epidemiología , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Satisfacción del Paciente/etnología , Prevalencia , Autoeficacia , Apoyo Social
20.
Ann Transplant ; 22: 121-127, 2017 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-28255157

RESUMEN

BACKGROUND The potential role of tissue damage factor high-mobility group box 1 (HMGB1) in islet cell transplantation is poorly understood. We investigated the role of HMGB1 in pancreatic islet cell isolation and culture in vitro and after pancreatic islet cell transplantation into diabetic nude mice in vivo. MATERIAL AND METHODS To generate damaged islets, isolated islets were treated with 1 mg/mL lipopolysaccharide (LPS). Some islets were pretreated with a neutralizing anti-HMGB1 antibody before LPS treatment to investigate the effect of HMGB1 on isolated islets damaged by LPS. Cell viability and insulin secretory function were analyzed 48 h after LPS and anti-HMGB1 antibody treatment. Streptozotocin-induced diabetes mice were injected with an anti-HMGB1 antibody 1 h prior to transplantation as a marginal islet mass. After transplantation, blood glucose levels were measured. RESULTS HMGB1 was more abundant in isolated islets than in other tissues, including pancreatic tissue. Anti-HMGB1 antibody pretreatment in LPS-treated islets improved cell viability and insulin secretory function and reduced the production of TNF-α and IL-1ß. Streptozotocin-induced diabetic mice treated with an anti-HMGB1 antibody after marginal mass islet cell transplantation recovered to normal blood glucose levels more rapidly and maintained their euglycemic status compared to controls. CONCLUSIONS HMGB1 plays a significant role in early loss of transplanted islet cells. Based on these results, the development of new drugs that inhibit HMGB1 secretion could improve the efficacy and efficiency of clinical islet cell transplantation.


Asunto(s)
Proteína HMGB1/metabolismo , Trasplante de Islotes Pancreáticos/métodos , Islotes Pancreáticos/metabolismo , Animales , Diabetes Mellitus Experimental/metabolismo , Masculino , Ratones , Ratones Desnudos , Ratas
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA