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1.
ACS Appl Mater Interfaces ; 16(3): 4013-4023, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38189267

RESUMEN

Electrical anisotropy, which is characterized by the efficient transmission of electrical signals in specific directions, is prevalent in both natural and engineered systems. However, traditional anisotropically conductive materials are often rigid and dry, thus limiting their utility in applications aiming for the seamless integration of various technologies with biological tissues. In the present study, we introduce a method for precisely controlling the microstructures of conductive and insulating polymers to create highly anisotropically conductive composite hydrogels. Our methodology involves combining aligned poly(vinyl alcohol) microfibrils, infused poly(3,4-ethylenedioxythiophene) polystyrenesulfonate, and sodium citrate precipitation to form dense, aligned conductive paths. This significantly enhances the electrical conductivity anisotropy (σ∥/σ⊥ ≈ 60.8) within these composite hydrogels.

2.
Adv Mater ; 35(52): e2307165, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37945054

RESUMEN

Unlike pigment-based colors, which are determined by their molecular structure, diverse colors can be expressed by a regular arrangement of nanomaterials. However, existing techniques for constructing such nanostructures have struggled to combine high precision and speed, resulting in a narrow gamut, and prolonged color fabrication time. Here, this work reports a phototunable mono ink that can generate a wide range of colors by controlling regularly arranged nanostructure. Core-shell growth controlled by polymerization time precisely regulates the distance between arranged particles at a nanometer-scale, enabling the generation of various colors. Moreover, the wide and thin arrangement induces constrained out-of-plane growth, thus facilitating the intricate color generation at the desired location via photopolymerization. Upon terminating polymerization by oxygen gas, the generated colors are readily fixed and kept stable. Utilizing programmed ultraviolet illumination, large-scale and high-resolution (≈1 µm) full-color printings are demonstrated at high speed (100 mm2 s-1 ).

3.
Small ; 19(9): e2205048, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36534830

RESUMEN

Repositioning is a common guideline for the prevention of pressure injuries of bedridden or wheelchair patients. However, frequent repositioning could deteriorate the quality of patient's life and induce secondary injuries. This paper introduces a method for continuous multi-site monitoring of pressure and temperature distribution from strategically deployed sensor arrays at skin interfaces via battery-free, wireless ionic liquid pressure sensors. The wirelessly delivered power enables stable operation of the ionic liquid pressure sensor, which shows enhanced sensitivity, negligible hysteresis, high linearity and cyclic stability over relevant pressure range. The experimental investigations of the wireless devices, verified by numerical simulation of the key responses, support capabilities for real-time, continuous, long-term monitoring of the pressure and temperature distribution from multiple sensor arrays. Clinical trials on two hemiplegic patients confined on bed or wheelchair integrated with the system demonstrate the feasibility of sensor arrays for a decrease in pressure and temperature distribution under minimal repositioning.


Asunto(s)
Líquidos Iónicos , Silla de Ruedas , Humanos , Temperatura , Tecnología Inalámbrica , Piel
4.
Soft Matter ; 18(35): 6487-6510, 2022 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-36000330

RESUMEN

Stretchable iontronics have recently been developed as an ideal interface to promote the interaction between humans and devices. Since the materials that use ions as charge carriers are typically transparent and stretchable, they have been used to fabricate devices with diverse functions with intrinsic transparency and stretchability. With the development of device design, material design has also been investigated to mitigate the issues associated with ionic materials, such as their weak mechanical properties, poor electrical properties, or poor environmental stabilities. In this review, we describe the recent progress on the design of materials in stretchable iontronics. By classifying stretchable ionic materials into three types of components (ionic conductors, ionic semiconductors, and ionic insulators), the issues each component has and the strategies to solve them are introduced, specifically in terms of molecular interactions. We then discuss the existing hurdles and challenges to be handled and shine light on the possibilities and opportunities from the insight of molecular interactions.

5.
Adv Mater ; 34(19): e2108586, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35245965

RESUMEN

Recent growing pursuit of skin-mountable devices has been impeded by the complicated structures of most sensing systems, containing electrode grids, stacked multilayers, and even external power sources. Here, a type of touch sensing, termed "triboresistive touch sensing", is introduced for gridless touch recognition based on monolayered ionic power generators. A homogeneous monolayer, i.e., ionic poly(dimethylsiloxane) (PDMS), generates electricity based on the electric field generated by touch. Voltages generated at each corner of the ionic PDMS rely on resistance between touch points and each corner, ensuring recognition of the touch positions without the need for electrode grid layers and external power sources. With notable advantages of high transparency (96.5%), stretchability (539.1%), and resilience (99.0%) of the ionic PDMS, epidermal triboresistive sensing is demonstrated to express touch position and readily play a musical instrument. A gridless system of triboresistive sensing allows rearrangement of the touch sections according to a given situation without any physical modification, and thus easily completes consecutive missions of controlling position, orientation, and gripping functions of a robot.

6.
Sci Adv ; 7(48): eabg9203, 2021 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-34818043

RESUMEN

Elasmobranch fishes, such as sharks, skates, and rays, use a network of electroreceptors distributed on their skin to locate adjacent prey. The receptors can detect the electric field generated by the biomechanical activity of the prey. By comparing the intensity of the electric fields sensed by each receptor in the network, the animals can perceive the relative positions of the prey without making physical contact. Inspired by this capacity for prey localization, we developed a soft artificial electroreceptor that can detect the relative positions of nearby objects in a noncontact manner by sensing the electric fields that originate from the objects. By wearing the artificial receptor, one can immediately receive spatial information of a nearby object via auditory signals. The soft artificial electroreceptor is expected to expand the ways we can perceive space by providing a sensory modality that did not evolve naturally in human beings.

7.
Nat Commun ; 11(1): 4638, 2020 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-32934209

RESUMEN

Existing gels are mostly polar, whose nature limits their role in soft devices. The intermolecular interactions of nonpolar polymer-liquid system are typically weak, which makes the gel brittle. Here we report highly soft and transparent nonpolar organogels. Even though their elements are only carbon and hydrogen, their elastic modulus, transparency, and stretchability are comparable to common soft hydrogels. A key strategy is introducing aromatic interaction into the polymer-solvent system, resulting in a high swelling ratio that enables efficient plasticization of the polymer networks. As a proof of applicability, soft perovskite nanocomposites are synthesized, where the nonpolar environment of organogels enables stable formation and preservation of highly concentrated perovskite nanocrystals, showing high photoluminescence efficiency (~99.8%) after water-exposure and environmental stabilities against air, water, acid, base, heat, light, and mechanical deformation. Their superb properties enable the demonstration of soft electroluminescent devices that stably emit bright and pure green light under diverse deformations.

8.
Adv Mater ; 32(37): e2001989, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32715525

RESUMEN

Conventional organic light-emitting devices without an encapsulation layer are susceptible to degradation when exposed to air, so realization of air-stable intrinsically-stretchable display is a great challenge because the protection of the devices against penetration of moisture and oxygen is even more difficult under stretching. An air-stable intrinsically-stretchable display that is composed of an intrinsically-stretchable electroluminescent device (SELD) integrated with a stretchable color-conversion layer (SCCL) that contains perovskite nanocrystals (PeNCs) is proposed. PeNCs normally decay when exposed to air, but they become resistant to this decay when dispersed in a stretchable elastomer matrix; this change is a result of a compatibility between capping ligands and the elastomer matrix. Counterintuitively, the moisture can efficiently passivate surface defects of PeNCs, to yield significant increases in both photoluminescence intensity and lifetime. A display that can be stretched up to 180% is demonstrated; it is composed of an air-stable SCCL that down-converts the SELD's blue emission and reemits it as green. The work elucidates the basis of moisture-assisted surface passivation of PeNCs and provides a promising strategy to improve the quantum efficiency of PeNCs with the aid of moisture, which allows PeNCs to be applied for air-stable stretchable displays.

9.
Materials (Basel) ; 12(13)2019 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-31247998

RESUMEN

In this study, a fabrication method of tapered microstructures with high aspect ratio was proposed by deep X-ray lithography. Tapered microstructures with several hundred micrometers and high aspect ratio are demanded owing to the high applicability in the fields of various microelectromechanical systems (MEMS) such as optical components and microfluidic channels. However, as the pattern and gap size were downsized to smaller micro-scale with higher aspect ratio over 5, microstructures were easily deformed or clustered together due to capillary force during the drying process. Here, we describe a novel manufacturing process of tapered microstructures with high aspect ratio. To selectively block the deep X-ray irradiation, an X-ray mask was prepared via conventional ultraviolet (UV) lithography. A double X-ray exposure process with and without X-ray mask was applied to impose a two-step dose distribution on a photoresist. For the clear removal of the exposed region, the product was developed in the downward direction, which encourages a gravity-induced pulling force as well as a convective transport of the developer. After a drying process with the surface additive, tapered microstructures were successfully fabricated with a pattern size of 130 µm, gap size of 40 µm, and aspect ratio over 7.

10.
Microbiol Res ; 193: 132-139, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27825481

RESUMEN

Very few bacterial species were identified as bio-herbicides for weed control. The present research was focused to elucidate the plant growth retardant properties of Enterobacter sp. I-3 during their interaction by determining the changes in endogenous photosynthetic pigments, plant hormones and amino acids. The two bacterial isolates I-4-5 and I-3 were used to select the superior bacterium for controlling weed seeds (Echinochloa crus-galli L. and Portulaca oleracea L.) germination. The post-inoculation of I-3 (Enterobacter sp. I-3) significantly inhibited the weeds seed germination than their controls. The mechanism of bacterium induced plant growth reduction was identified in lettuce treated with I-3 bacterium and compared their effects with known chemical herbicide, trinexapac-ethyl (TE). The treatment of I-3 and TE showed a significant inhibitory effect on shoot length, leaf number, leaf length, leaf width, shoot weight, root weight and chlorophyll content in lettuce seedlings. The endogenous gibberellins (GAs) and abscisic acid (ABA) analysis showed that Enterobacter sp. I-3 treated plants had lower levels of GAs (GA12, GA19, GA20 and GA8) and GAs/ABA ratio and then, the higher level of ABA when compared to their controls. Indeed, the individual amino acids ie., aspartic acid, glutamic acid, glycine, threonine, alanine, serine, leucine, isoleucine and tyrosine were declined in TE and I-3 exposed plants. Our results suggest that the utilization of Enterobacter sp. I-3 inhibits the GAs pathway and amino acids synthesis in weeds to control their growth can be an alternative to chemical herbicides.


Asunto(s)
Ácido Abscísico/metabolismo , Aminoácidos/metabolismo , Echinochloa/crecimiento & desarrollo , Enterobacter/metabolismo , Giberelinas/antagonistas & inhibidores , Desarrollo de la Planta , Portulaca/crecimiento & desarrollo , Echinochloa/microbiología , Herbicidas/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Portulaca/microbiología
11.
Clin Endosc ; 49(3): 273-81, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26942581

RESUMEN

BACKGROUND/AIMS: Delayed post-endoscopic submucosal dissection (ESD) bleeding (DPEB) is difficult to predict and there is controversy regarding the usefulness of prophylactic hemostasis during second-look endoscopy. This study evaluated the risk factors related to DPEB, the relationship between clinical outcomes and the Forrest classification, and the results of prophylactic hemostasis during second-look endoscopy. METHODS: Second-look endoscopy was performed on the day after ESD to check for recent hemorrhage or potential bleeding and the presence of artificial ulcers in all patients. RESULTS: DPEB occurred in 42 of 581 patients (7.2%). Multivariate analysis determined that a specimen size ≥40 mm (odds ratio [OR], 3.03; p=0.003), and a high-risk Forrest classification (Forrest Ib+IIa+IIb; OR, 6.88; p<0.001) were risk factors for DPEB. DPEB was significantly more likely in patients classified with Forrest Ib (OR, 24.35; p<0.001), IIa (OR, 12.91; p<0.001), or IIb (OR, 8.31; p<0.001) ulcers compared with Forrest III ulcers. There was no statistically significant difference between the prophylactic hemostasis and non-hemostasis groups (Forrest Ib, p=0.938; IIa, p=0.438; IIb, p=0.397; IIc, p=0.773) during second-look endoscopy. CONCLUSIONS: The Forrest classification of artificial gastric ulcers during second-look endoscopy seems to be a useful tool for predicting delayed bleeding. However, routine prophylactic hemostasis during second-look endoscopy seemed to not be useful for preventing DPEB.

12.
Indian J Microbiol ; 55(2): 207-212, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25805908

RESUMEN

Development of bio-herbicides is an emerging method to weed management in agricultural field. Very few studies were conducted on identification of microbial bio-herbicides to weed control. The present study was aimed to isolate and identify the effective bio-herbicide potential bacterium from soil and assess their role on plant growth inhibition. Three-hundred and one rhizobacteria were isolated from agriculture field soil samples collected from various parts of Republic of Korea. Two bacterial strains, I-4-5 and I-3 were significantly reduced the seedling growth of radish when compared to their controls. The highest rate of seedling growth inhibition was observed in I-3 bacterial isolate treatment in lettuce and radish. The mechanism of an effective bio-herbicide I-3 to plant growth inhibition was determined by analyzing IAA in their culture medium. IAA biosynthesis pathway of Enterobacter sp. I-3 was identified as tryptophan-dependent pathway and its production was increased due to addition of tryptophan in culture medium as quantified by using GC-MS SIM. In an in vitro study revealed that I-3 bacterial culture exudate combined with tryptophan significantly decreased leaf length, leaf width, root length and increased the number of lateral roots of lettuce. Indeed, the genomic DNA of I-3 bacterium was isolated and 16S rDNA was sequenced to find out the name of the bacterium. Based on phylogenetic analysis, I-3 isolate was identified and named into Enterobacter sp. I-3. The results of this study suggest that the utilization of Enterobacter sp. I-3 to crop field can be act as a potential bio-herbicide against weed growth.

13.
Plant Physiol Biochem ; 84: 115-124, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25270162

RESUMEN

The physiological changes in tolerant soybean plants under salt and drought stress conditions with Pseudomonas putida H-2-3 were investigated. A bacterial isolate H-2-3 was isolated from soil and identified as Pseudomonas putida H-2-3 by 16S rDNA sequences. The treatment of P. putida H-2-3 significantly increased the length, fresh and dry weight of shoot and chlorophyll content in gibberellins (GAs) deficient mutant Waito-c rice seedlings over the control, it might be the presence of GA1, GA4, GA9 and GA20. The soybean plant growth was retarded in salt (120 mM sodium chloride) and drought (15% polyethylene glycol) stress conditions at 10 days treatments, while P. putida H-2-3 effectively enhanced the shoot length and fresh weight of plants suffered at salt and drought stress. The chlorophyll content was lower in abiotic stress conditions and bacterial inoculant P. putida H-2-3 mitigated the stress effects by an evidence of higher quantity of chlorophyll content in plants exposed to salt and drought. The stress hormonal analysis revealed that individual treatment of P. putida H-2-3, salt and drought significantly enhanced the abscisic acid and salicylic acid content than their control. P. putida H-2-3 applied to salt and drought stressed plants showed a lower level of abscisic acid and salicylic acid and a higher level of jasmonic acid content. Under stress condition induced by salt and drought in plants expressed higher level of total polyphenol, superoxide dismutase and radical scavenging activity and no significant changes in flavonoids. The bio-inoculant, P. putida H-2-3 modulated those antioxidants by declining superoxide dismutase, flavonoids and radical scavenging activity. P. putida H-2-3 induced tolerance against abiotic stress was confirmed by a reduction of Na content in abiotic stressed plants. The results suggest that P. putida H-2-3 application reprograms the chlorophyll, stress hormones and antioxidants expression in abiotic stress affected soybean plant and improves their growth under stress environment.


Asunto(s)
Giberelinas/metabolismo , Glycine max/metabolismo , Glycine max/microbiología , Pseudomonas putida/fisiología , Rhizobium/fisiología , Antioxidantes/metabolismo , Sequías , Reguladores del Crecimiento de las Plantas/metabolismo , Pseudomonas putida/metabolismo , Rhizobium/metabolismo , Cloruro de Sodio/farmacología
14.
Korean J Gastroenterol ; 63(4): 223-30, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24755747

RESUMEN

BACKGROUND/AIMS: There are few data supporting the diagnostic yield of brush cytology depending on the order of cytologic preparation method or the location or shape of tumors in biliary strictures. We investigated diagnostic yields and variations in brush cytology with direct smear and cell-block preparations according to sampling preparation sequence and tumor location and shape in biliary strictures. METHODS: Patients who had undergone ERCP with tissue sampling between August 2009 and April 2013 were analyzed retrospectively. Group A was examined using brush cytology with direct smear followed by cell-block with or without biopsy, while the reverse order was performed for group B. RESULTS: Among 138 enrolled patients, 92 patients (A: 36, B: 56) underwent both brush cytology with direct smear and cell-block preparations. No differences in sensitivity, specificity, or accuracy were observed according to the sampling preparation method and the location or shape of tumors in biliary strictures. The cellularity observed from brush cytology with direct smear was better than that from cell-block according to the location of the tumor (p<0.01). The diagnostic yield was increased in both groups with addition of an endobiliary biopsy. CONCLUSIONS: No difference in diagnostic accuracy was observed between the sequences of preparation for brush cytology with direct smear and cell-block techniques. Brush cytology showed better cellularity for diagnosis.


Asunto(s)
Neoplasias de los Conductos Biliares/patología , Citodiagnóstico , Anciano , Anciano de 80 o más Años , Colangiocarcinoma/patología , Colangiopancreatografia Retrógrada Endoscópica , Femenino , Neoplasias de la Vesícula Biliar/patología , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Pancreáticas/patología , Estudios Retrospectivos , Sensibilidad y Especificidad
15.
Cancer Med ; 3(4): 1041-51, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24729479

RESUMEN

Our earlier work showed that knockout of hematopoietic prostaglandin D synthase (HPGDS, an enzyme that produces prostaglandin D2) caused more adenomas in Apc(Min/+) mice. Conversely, highly expressed transgenic HPGDS allowed fewer tumors. Prostaglandin D2 (PGD2) binds to the prostaglandin D2 receptor known as PTGDR (or DP1). PGD2 metabolites bind to peroxisome proliferator-activated receptor γ (PPARG). We hypothesized that Ptgdr or Pparg knockouts may raise numbers of tumors, if these receptors take part in tumor suppression by PGD2. To assess, we produced Apc(Min/+) mice with and without Ptgdr knockouts (147 mice). In separate experiments, we produced Apc(Min/+) mice expressing transgenic lipocalin-type prostaglandin D synthase (PTGDS), with and without heterozygous Pparg knockouts (104 mice). Homozygous Ptgdr knockouts raised total numbers of tumors by 30-40% at 6 and 14 weeks. Colon tumors were not affected. Heterozygous Pparg knockouts alone did not affect tumor numbers in Apc(Min/+) mice. As mentioned above, our Pparg knockout assessment also included mice with highly expressed PTGDS transgenes. Apc(Min/+) mice with transgenic PTGDS had fewer large adenomas (63% of control) and lower levels of v-myc avian myelocytomatosis viral oncogene homolog (MYC) mRNA in the colon. Heterozygous Pparg knockouts appeared to blunt the tumor-suppressing effect of transgenic PTGDS. However, tumor suppression by PGD2 was more clearly mediated by receptor PTGDR in our experiments. The suppression mechanism did not appear to involve changes in microvessel density or slower proliferation of tumor cells. The data support a role for PGD2 signals acting through PTGDR in suppression of intestinal tumors.


Asunto(s)
Adenoma/genética , Neoplasias Intestinales/genética , Prostaglandina D2/fisiología , Receptores Inmunológicos/metabolismo , Receptores de Prostaglandina/metabolismo , Adenoma/metabolismo , Adenoma/patología , Proteína de la Poliposis Adenomatosa del Colon/genética , Proteína de la Poliposis Adenomatosa del Colon/metabolismo , Animales , Femenino , Expresión Génica , Humanos , Neoplasias Intestinales/metabolismo , Neoplasias Intestinales/patología , Oxidorreductasas Intramoleculares , Isomerasas/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , PPAR gamma/genética , Prostaglandina-Endoperóxido Sintasas/genética , Prostaglandina-Endoperóxido Sintasas/metabolismo , Receptores Inmunológicos/genética , Receptores de Prostaglandina/genética , Carga Tumoral , Proteínas Supresoras de Tumor/genética , Proteínas Supresoras de Tumor/metabolismo
16.
Prostaglandins Other Lipid Mediat ; 97(1-2): 22-8, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21821144

RESUMEN

Intestinal tumors in Apc(Min/+) mice are suppressed by over-production of HPGDS, which is a glutathione transferase that forms prostaglandin D(2) (PGD(2)). We characterized naturally occurring HPGDS isoenzymes, to see if HPGDS variation is associated with human colorectal cancer risk. We used DNA heteroduplex analysis and sequencing to identify HPGDS variants among healthy individuals. HPGDS isoenzymes were produced in bacteria, and their catalytic activities were tested. To determine in vivo effects, we conducted pooled case-control analyses to assess whether there is an association of the isoenzyme with colorectal cancer. Roughly 8% of African Americans and 2% of Caucasians had a highly stable Val187lle isoenzyme (with isoleucine instead of valine at position 187). At 37°C, the wild-type enzyme lost 15% of its activity in 1h, whereas the Val187Ile form remained >95% active. At 50°C, the half life of native HPGDS was 9min, compared to 42 min for Val187Ile. The odds ratio for colorectal cancer among African Americans with Val187Ile was 1.10 (95% CI, 0.75-1.62; 533 cases, 795 controls). Thus, the Val187Ile HPGDS isoenzyme common among African Americans is not associated with colorectal cancer risk. Other approaches will be needed to establish a role for HPGDS in occurrence of human intestinal tumors, as indicated by a mouse model.


Asunto(s)
Sustitución de Aminoácidos , Negro o Afroamericano/genética , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/genética , Predisposición Genética a la Enfermedad/genética , Oxidorreductasas Intramoleculares/química , Oxidorreductasas Intramoleculares/genética , Lipocalinas/química , Lipocalinas/genética , Adulto , Animales , Estudios de Casos y Controles , Neoplasias Colorrectales/etnología , Estabilidad de Enzimas , Técnicas de Inactivación de Genes , Humanos , Oxidorreductasas Intramoleculares/deficiencia , Isoenzimas/química , Isoenzimas/deficiencia , Isoenzimas/genética , Ratones , Modelos Moleculares , Conformación Proteica , Transgenes/genética
17.
Cancer Res ; 67(3): 881-9, 2007 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-17283118

RESUMEN

Aspirin and other nonsteroidal anti-inflammatory drugs prevent some cases of colon cancer by inhibiting prostaglandin (PG) synthesis. PGE(2) promotes colon neoplasia, as shown by knockout mouse studies on enzymes and receptors in the PG cascade. A few experiments 20 to 30 years ago suggested that PGD(2) may suppress tumors, but a role for biosynthetic enzymes for PGD(2) in tumor development has not been studied. We report here that disruption of the gene for hematopoietic PGD synthase in Apc(Min/+) mice led to approximately 50% more intestinal adenomas compared with controls. Tumor size was not affected. By immunohistochemistry, we detected hematopoietic PGD synthase mainly in macrophages and monocytes of the gut mucosa. The mean number of tumors did not increase with knockout of the gene for the lipocalin type of the enzyme, which is not produced in the intestine. On the other hand, Apc(Min/+) mice with transgenic human hematopoietic PGD synthase tended to have 80% fewer intestinal adenomas. The transgene produced high mRNA levels (375-fold over endogenous). There was a suggestion of higher urinary excretion of 11beta-PGF(2alpha) and a lower excretion of a PGE(2) metabolite in transgenic mice, but differences (30-40%) were not statistically significant. The results support an interpretation that hematopoietic PGD synthase controls an inhibitory effect on intestinal tumors. Further studies will be needed to prove possible mechanisms, such as routing of PG production away from protumorigenic PGE(2) or inhibition of the nuclear factor-kappaB cascade by PGD(2) metabolites.


Asunto(s)
Poliposis Adenomatosa del Colon/enzimología , Sistema Hematopoyético/enzimología , Oxidorreductasas Intramoleculares/deficiencia , Oxidorreductasas Intramoleculares/metabolismo , Poliposis Adenomatosa del Colon/genética , Poliposis Adenomatosa del Colon/orina , Animales , Dinoprost/orina , Femenino , Oxidorreductasas Intramoleculares/biosíntesis , Oxidorreductasas Intramoleculares/genética , Lipocalinas , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Prostaglandina D2/biosíntesis , Prostaglandinas/orina
18.
Pediatr Nephrol ; 19(3): 295-9, 2004 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-14758530

RESUMEN

We investigated the association between IL-1beta, IL-1ra, and TNF-alpha gene polymorphisms and childhood nephrotic syndrome (NS). We analyzed the genetic polymorphism of IL-1beta, IL-1ra, and TNF-alpha genes in 152 patients with childhood NS and 292 healthy adult controls. The C to T exchange at position -511 of IL-1beta and the G to A at -308 of the TNF-alpha gene were genotyped. Five alleles of the IL-1ra gene were identified and designated as IL1RN*1, IL1RN*2, IL1RN*3, IL1RN*4, and IL1RN*5, according to the variable number of tandem repeats in intron 2. The allele frequencies of IL-1beta1 (-511C), IL-1beta2 (-511T), TNF1 (-308G), and TNF2 (-308A) were 53.0, 47.0, 92.1, and 7.9%, respectively, in the childhood NS group. This was not significantly different from normal controls. In the childhood NS group, the allele frequencies of IL1RN*1, IL1RN*2, IL1RN*3, IL1RN*4, and IL1RN*5 were 90.8, 7.6, 1.6, 0, and 0% [IL1RN*1 odds ratio (OR)=0.296, P=0.0001, IL1RN*2 OR=3.902, P=0.0002]. A high allele frequency of IL1RN*2 and a lower allele frequency of IL1RN*1 were found in childhood NS, although there was no association with IL-1beta and TNF-alpha. A high allele frequency of the IL1RN*2 allele may affect disease susceptibility in childhood NS.


Asunto(s)
Interleucina-1/genética , Síndrome Nefrótico/genética , Polimorfismo Genético , Sialoglicoproteínas/genética , Factor de Necrosis Tumoral alfa/genética , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Proteína Antagonista del Receptor de Interleucina 1 , Masculino , Persona de Mediana Edad
19.
Biochim Biophys Acta ; 1649(1): 16-23, 2003 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-12818186

RESUMEN

Glutathione transferases (GSTs) are a family of enzymes that detoxify electrophilic compounds, such as carcinogens or drugs, by conjugating them to glutathione. The enzymes have contributed to the understanding of protein structure, due to large differences in amino acid sequence within the family, yet similar architecture and folding. Our objective was to conduct a systematic survey of GSTP1 polymorphisms and their function. Nearly all variants detected were known polymorphisms: IVS4+13C>A; Ile105Val; Ala114Val; and g.2596T>C (Ser185Ser). However, we also found a novel Phe151Leu substitution in an African-American subject (1 out of 111). Kinetic parameters for the conjugation reaction with 1-chloro-2,4-dinitrobenzene (CDNB) were determined for the novel variant enzyme purified via heterologous expression in Escherichia coli. Five substrates were used for measurement of specific activities, including isothiocyanate compounds that occur in cruciferous vegetables (benzylisothiocyanate, phenethylisothiocyanate, and sulforaphane). Such isothiocyanate substrates are potential cancer chemopreventive agents that are conjugated by GSTs. No major change in kinetic parameters was observed. However, the half-life at 50 degrees C of the Leu 151 enzyme was reduced to 12 min, as compared to 28 min for the Phe 151 enzyme. Residue 151 is located at the N-terminus of helix alpha6 in GST motif II, surrounded by hydrophobic residues, and near the conserved "hydrophobic staple" and N-capping box motifs. These local structural elements aid in formation of helix alpha6 and promote proper folding and protein stability. Analysis of the three-dimensional structure showed that substitution of Phe 151 with Leu produces a hydrophobic cavity in the GSTP1 core, thereby destabilizing its structure. Phe151Leu represents one of the first-described allelic variations in a protein folding motif.


Asunto(s)
Glutatión Transferasa/química , Glutatión Transferasa/genética , Isoenzimas/química , Isoenzimas/genética , Secuencias de Aminoácidos , Sustitución de Aminoácidos , Población Negra/genética , Dinitroclorobenceno/metabolismo , Estabilidad de Enzimas/genética , Variación Genética , Gutatión-S-Transferasa pi , Glutatión Transferasa/metabolismo , Semivida , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Isoenzimas/metabolismo , Cinética , Leucina/genética , Modelos Moleculares , Fenilalanina/genética , Polimorfismo Genético , Pliegue de Proteína
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