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1.
Anal Chem ; 94(9): 3872-3880, 2022 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-35179372

RESUMEN

There have been tremendous innovations in microfluidic clinical diagnostics to facilitate novel point-of-care testing (POCT) over the past decades. However, the automatic operation of microfluidic devices that minimize user intervention still lacks reliability and repeatability because microfluidic errors such as bubbles and incomplete filling pose a major bottleneck in commercializing the microfluidic devices for clinical testing. In this work, for the first time, various states of microfluid were recognized to control immunodiagnostics by artificial intelligence (AI) technology. The developed AI-controlled microfluidic platform was operated via an Android smartphone, along with a low-cost polymer device to effectuate enzyme-linked immunosorbent assay (ELISA). To overcome the limited machine-learning capability of smartphones, the region-of-interest (ROI) cascading and conditional activation algorithms were utilized herein. The developed microfluidic chip was incorporated with a bubble trap to remove any bubbles detected by AI, which helps in preventing false signals during immunoassay, as well as controlling the reagents' movement with an on-chip micropump and valve. Subsequently, the developed immunosensing platform was tested for conducting real ELISA using a single microplate from the 96-well to detect the Human Cardiac Troponin I (cTnI) biomarker, with a detection limit as low as 0.98 pg/mL. As a result, the developed platform can be envisaged as an AI-based revolution in microfluidics for point-of-care clinical diagnosis.


Asunto(s)
Dispositivos Laboratorio en un Chip , Técnicas Analíticas Microfluídicas , Inteligencia Artificial , Automatización , Humanos , Inmunoensayo , Reproducibilidad de los Resultados , Teléfono Inteligente
2.
Molecules ; 27(16)2022 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-36014395

RESUMEN

Averrhoa carambola L. is reported for its anti-obese and anti-diabetic activities. The present study aimed to investigate its aqueous methanol leaf extract (CLL) in vivo anti-obese activity along with the isolation and identification of bioactive compounds and their in vitro α-glucosidase inhibition assessment. CLL improved all obesity complications and exhibited significant activity in an obese rat model. Fourteen compounds, including four flavone glycosides (1-4) and ten dihydrochalcone glycosides (5-12), were isolated and identified using spectroscopic techniques. New compounds identified in planta included (1) apigenin 6-C-(2-deoxy-ß-D-galactopyranoside)-7-O-ß-D-quinovopyranoside, (8) phloretin 3'-C-(2-O-(E)-cinnamoyl-3-O-ß-D-fucopyranosyl-4-O-acetyl)-ß-D-fucopyranosyl-6'-O-ß-D fucopyranosyl-(1/2)-α-L arabinofuranoside, (11a) phloretin3'-C-(2-O-(E)-p-coumaroyl-3-O-ß-D-fucosyl-4-O-acetyl)-ß-D-fucosyl-6'-O-(2-O-ß-D-fucosyl)-α-L-arabinofuranoside, (11b) phloretin3'-C-(2-O-(Z)-p-coumaroyl-3-O-ß-D-fucosyl-4-O-acetyl)-ß-D-fucosyl-6'-O-(2-O-ß-D-fucosyl)-α-L-arabinofuranoside. Carambolaside M (5), carambolaside Ia (6), carambolaside J (7), carambolaside I (9), carambolaside P (10a), carambolaside O (10b), and carambolaside Q (12), which are reported for the first time from A. carambola L. leaves, whereas luteolin 6-C-α-L-rhamnopyranosyl-(1-2)-ß-D-fucopyranoside (2), apigenin 6-C-ß-D-galactopyranoside (3), and apigenin 6-C-α-L-rhamnopyranosyl-(1-2)-ß-L-fucopyranoside (4) are isolated for the first time from Family. Oxalidaceae. In vitro α-glucosidase inhibitory activity revealed the potential efficacy of flavone glycosides, viz., 1, 2, 3, and 4 as antidiabetic agents. In contrast, dihydrochalcone glycosides (5-11) showed weak activity, except for compound 12, which showed relatively strong activity.


Asunto(s)
Averrhoa , Leucemia Linfocítica Crónica de Células B , Animales , Apigenina , Averrhoa/química , Galactosa , Inhibidores de Glicósido Hidrolasas/farmacología , Glicósidos/química , Hojas de la Planta , Polifenoles/farmacología , Ratas , alfa-Glucosidasas
3.
Anal Chem ; 93(16): 6394-6402, 2021 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-33830748

RESUMEN

Herein, we have developed a fully automated optofluidic device to execute enzyme-linked immunosorbent assay (ELISA) using an active 96-well hybrid lab-on-a-chip (LOC) device. To automate the solution loading into the reaction zone of the device and the post-assayed signal analysis, laser irradiation-induced image whitening was utilized with a smartphone-based optical platform. Two optical phenomena were utilized in our platform to detect the liquid in the reaction chamber using a smartphone. First, by Fresnel's equation, the refraction difference between air and water resulted in the intensity change of the reflected light from the reaction chamber. Therefore, when the liquid was entering into the reaction chamber, the intensity of the reflected light was changed. Second, when the light intensity increases, the smartphone-captured image whitens out due to saturation, even when the red color light was incident. Therefore, by measuring the RGB value of the smartphone image, the intensity changes by the liquid movement in the reaction chamber were successfully monitored. Our platform showed a low detection limit of 7.81 pg/mL for the detection of the NT-proBNP human cardiac biomarker with almost a half standard deviation, compared to the manually operated LOC-based ELISA. As a fully automated LOC adopting a conventional 96-well ELISA platform, we thus concluded that the developed platform can be widely applied for point-of-care clinical tests.

4.
Climacteric ; 23(4): 397-403, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32299254

RESUMEN

Objective: This study aimed to compare efficacy and safety of lidocaine versus tramadol versus placebo in reducing the pain of diagnostic outpatient hysteroscopy (OH) in postmenopausal women.Materials and methods: This randomized double-blinded study included 156 menopausal women who received intrauterine lidocaine infusion or oral tramadol (50 mg) or placebo before diagnostic OH (52 women/group). Primary outcome was pain severity during the procedure using a 10-cm visual analog scale. Secondary outcomes were pain scores 10 and 30 min post procedure, satisfaction level, and ease of cervical entry.Results: Lidocaine had lower pain scores compared to placebo during and 10 min after the procedure (p < 0.001). Tramadol had lower pain scores than placebo during the procedure (p = 0.04), 10 min after the procedure (p = 0.03), and 30 min after the procedure (p = 0.04). Both lidocaine and tramadol resulted in an easier procedure than placebo (p < 0.001 and p = 0.04, respectively). Lidocaine had an easier cervical entry compared to tramadol (p = 0.004). Satisfaction scores in the lidocaine and tramadol groups were significantly higher than in the placebo group (p < 0.001).Conclusions: Lidocaine and tramadol were effective in reducing postmenopausal women-reported pain during and after diagnostic OH. However, lidocaine was better than tramadol in facilitating hysteroscope passage through the cervical canal and the reduction in pain levels with lidocaine was clinically relevant.Trial registration number: NCT03701984.


Asunto(s)
Analgésicos/uso terapéutico , Lidocaína/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Asociado a Procedimientos Médicos/tratamiento farmacológico , Tramadol/uso terapéutico , Procedimientos Quirúrgicos Ambulatorios/efectos adversos , Procedimientos Quirúrgicos Ambulatorios/métodos , Método Doble Ciego , Femenino , Humanos , Histeroscopía/efectos adversos , Histeroscopía/métodos , Persona de Mediana Edad , Manejo del Dolor/métodos , Dimensión del Dolor , Dolor Postoperatorio/etiología , Dolor Asociado a Procedimientos Médicos/etiología , Posmenopausia , Estudios Prospectivos , Resultado del Tratamiento
5.
Molecules ; 25(10)2020 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-32455938

RESUMEN

Averrhoa carambola L. is a tropical tree with edible fruit that grows at different climatic conditions. Despite its nutritive value and reported health benefits, it is a controversial fruit owing to its rich oxalate content. The present study aimed at investigating aroma and nutrient primary metabolites distribution in A. carambola fruits grown in Indonesia, Malaysia (its endemic origin) versus Egypt, and at different ripening stages. Two techniques were employed to assess volatile and non-volatile metabolites including headspace solid-phase micro-extraction (HS-SPME) joined with gas chromatography coupled with mass-spectrometry (GC-MS) and GC-MS post silylation, respectively. Twenty-four volatiles were detected, with esters amounting for the major class of volatiles in Egyptian fruit at ca. 66%, with methyl caproate as the major component, distinguishing it from other origins. In contrast, aldehydes predominated tropically grown fruits with the ether myristicin found exclusively in these. Primary metabolites profiling led to the identification of 117 metabolites viz. sugars, polyols and organic acids. Fructose (38-48%) and glucose (21-25%) predominated sugar compositions in ripe fruits, whereas sorbitol was the major sugar alcohol (2.4-10.5%) in ripe fruits as well. Oxalic acid, an anti-nutrient with potential health risks, was the major organic acid detected in all the studied fruits (1.7-2.7%), except the Malaysian one (0.07%). It increases upon fruit ripening, including considerable amounts of volatile oxalate esters detected via SPME, and which must not be omitted in total oxalate determinations for safety assessments.


Asunto(s)
Averrhoa/metabolismo , Metaboloma , Nutrientes/metabolismo , Compuestos Orgánicos Volátiles/metabolismo , Averrhoa/química , Egipto , Ésteres/química , Frutas/química , Cromatografía de Gases y Espectrometría de Masas , Humanos , Malasia , Nutrientes/química , Odorantes/análisis , Compuestos Orgánicos Volátiles/química
6.
Mol Cell ; 35(6): 818-29, 2009 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-19782031

RESUMEN

The CHK2 protein kinase is an important transducer of DNA damage checkpoint signals, and its mutation contributes to hereditary and sporadic cancer. CHK2 activation is triggered by the phosphorylation of Thr68 by the DNA damage-activated ATM kinase. This leads to transient CHK2 dimerization, in part through intermolecular phosphoThr68-FHA domain interactions. Dimerization promotes kinase activation through activation-loop autophosphorylation, but the mechanism of this process has not been clear. The dimeric crystal structure of CHK2, described here, in conjunction with biochemical and mutational data reveals that productive CHK2 dimerization additionally involves intermolecular FHA-kinase domain and FHA-FHA interactions. Ile157, mutated in the Li-Fraumeni cancer-predisposition syndrome, plays a central role in the FHA-kinase domain interface, explaining the lack of dimerization and autophosphorylation of this mutant. In the dimer, the kinase active sites face each other in close proximity, indicating that dimerization may also serve to optimally position the kinase active sites for efficient activation loop transphosphorylation.


Asunto(s)
Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas de la Ataxia Telangiectasia Mutada , Proteínas de Ciclo Celular/metabolismo , Quinasa de Punto de Control 2 , Cristalografía por Rayos X , Proteínas de Unión al ADN/metabolismo , Activación Enzimática , Humanos , Isoleucina , Síndrome de Li-Fraumeni/enzimología , Síndrome de Li-Fraumeni/genética , Modelos Moleculares , Mutagénesis Sitio-Dirigida , Mutación , Fosforilación , Conformación Proteica , Multimerización de Proteína , Proteínas Serina-Treonina Quinasas/química , Proteínas Serina-Treonina Quinasas/genética , Estructura Terciaria de Proteína , Proteínas Recombinantes/metabolismo , Relación Estructura-Actividad , Treonina/metabolismo , Proteínas Supresoras de Tumor/metabolismo
7.
Biomater Sci ; 12(20): 5203-5214, 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39240173

RESUMEN

The blood-based detection of Alzheimer's disease (AD) is becoming challenging since the blood-brain barrier (BBB) restricts the direct circulation of AD molecules in the blood, thereby precluding the detection of AD at an early-stage. Herein, we report the development of a novel CNT-metal-porous graphene hybrid (CNT-MGH) nano-interdigitated array (n-IDA) electrochemical 8-well biosensor for the successful early-stage diagnosis of AD from blood. Laser-induced graphene (LIG) technology has been used to fabricate the proposed CNT-MGH n-IDA 8-well sensor. Firstly, the electrochemical characterization (i.e., electrode gap, material composition, etc.) of the proposed sensor was demonstrated by measuring p-aminophenol (PAP) with a limit of detection (LOD) of 0.1 picomole. Subsequently, the CNT-MGH n-IDA 8-well sensor was then used to diagnose AD via novel blood biomarkers p-Tau 217 and p-Tau 181 using an electrochemical enzyme-linked immunosorbent assay (e-ELISA) enzyme by-product PAP. During e-ELISA, the alkaline phosphatase enzyme (IgG-AP) tagged to the detection antibody produced an electroactive ELISA by-product PAP by reacting with the enzyme-substrate 4-aminophenyl phosphate (PAPP). Finally, the CNT-MGH n-IDA 8-well sensor was then used to measure the current generated by the redox reaction via the e-ELISA by-product PAP. While quantified, the proposed CNT-MGH n-IDA 8-well sensor successfully detected p-Tau 217 and p-Tau 181 proteins in blood with LODs of 0.16 pg ml-1 and 0.08 pg ml-1, respectively.


Asunto(s)
Enfermedad de Alzheimer , Aminofenoles , Técnicas Biosensibles , Técnicas Electroquímicas , Grafito , Límite de Detección , Grafito/química , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/sangre , Técnicas Biosensibles/instrumentación , Humanos , Técnicas Electroquímicas/instrumentación , Aminofenoles/química , Nanotubos de Carbono/química , Ensayo de Inmunoadsorción Enzimática , Proteínas tau/sangre , Proteínas tau/análisis , Biomarcadores/sangre , Electrodos
8.
Small Methods ; : e2400189, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38958066

RESUMEN

The increasing demand for electric vehicles necessitates the development of cost-effective, mass-producible, long-lasting, and highly conductive batteries. Making this kind of battery is exceedingly tricky. This study introduces an innovative fabrication technique utilizing a laser-induced graphene (LIG) approach on commercial Kapton film to create hexagonal pores. These pores form vertical conduction paths for electron and ion transportation during lithiation and delithiation, significantly enhancing conductivity. The nongraphitized portion of the Kapton film makes it a binder-less, free-standing electrode, providing mechanical stability. Various analytical techniques, including scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), Raman spectroscopy, and atomic force microscopy (AFM) are utilized to confirm the transformation of a 3D porous graphene sheet from a commercial Kapton film. Cross-sectional SEM images verify the vertical connections. The specific capacity of 581 mAh g-1 is maintained until the end, with 99% coulombic efficiency at 0.1C. This simple manufacturing method paves the pathway for future LIG-based, cost-effective, lightweight, mass-producible, long-lasting, vertically conductive electrodes for lithium-ion batteries.

9.
Jpn J Vet Res ; 61 Suppl: S41-3, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23631151

RESUMEN

This study was conducted to establish the potential of lettuce (Lactuca sativa L. var. buttercrunch) seeds as a bioindicator (BI), or a biological tool for detecting the presence of some toxic materials used in tanning industry and determining their concentrations using the germination percentage as a parameter (indicator). Samples of Gezira Tannery Corporation (GTC) wastewater (WW) were collected from both the mouth and the tail of the drainage stream. Lettuce seeds (10/Petri dish, replicated 3x and each experiment was repeated 3x) were treated by GTC WW and other important tanning agents (chromium oxide, sodium sulfide, Preventol WB) in solution using different concentrations of each and their mixture. The bioassay experiment revealed that the seeds were intoxicated (i.e. reduced the germination percentage), when exposed to the WW. On exposure to several concentrations from each input, the concentrations that can be measured by this BI (i.e. sensitivity and reliability) are: chromium oxide from 0.1 to 3.25%, sodium sulfide from 0.19 to 1.5% and Preventol WB from 18.75 to 150 ppm. Lower concentrations cannot be measured, and higher concentrations resulted in 100% inhibition. The IC50 was determined by probit analysis for the WW, mixture of the three inputs, chromium oxide alone, sodium sulfide alone and Preventol WB alone were: 35.5, 14.5, 0.44, 0.45 and 0.005%, respectively. The slopes of the log-dose probability lines (Ld-P) showed that this BI response to all treatments was homogeneous (> 2) (tabulated X2 (df = n - 2) at 5% = 0.172, 0.11, 0.064, 0.05 and 0.05). It is concluded that lettuce seeds satisfy almost all the required properties of the ideal BI.


Asunto(s)
Residuos Industriales/efectos adversos , Lactuca/efectos de los fármacos , Semillas/efectos de los fármacos , Curtiembre , Eliminación de Residuos Líquidos/métodos , Bioensayo , Relación Dosis-Respuesta a Droga , Lactuca/crecimiento & desarrollo , Semillas/crecimiento & desarrollo
10.
Toxicol Mech Methods ; 23(4): 263-72, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23193971

RESUMEN

Cadmium has been classified as an environmental pollutant and human carcinogen. Pectin is a family of complex polysaccharides that function as hydrating agents and cementing materials for the cellulosic network. The aim of this study was to evaluate the protective role of pectin against cadmium-induced testicular toxicity and oxidative stress in rats. Forty male Wistar rats were divided into five equal groups. Groups 1 and 2 were injected intraperitoneally (i.p.) saline (1 mg/kg) and pectin (50 mg/kg), respectively, two days/weeks over three weeks period. Groups 3-5 were injected i.p. with 1 mg/kg cadmium two days/week while groups 4 and 5 co-administrated i.p. with 25 and 50 mg/kg pectin, respectively, three days/week over three weeks period. The results of the present work revealed that cadmium-exposed rats showed decrease in serum testosterone, dehydroepiandrosterone sulfate and lactate dehydrogenase. Testicular cholesterol, total protein, glucose-6-phosphate dehydrogenase, 3ß-hydroxysteroid dehydrogenase, superoxide dismutase, glutathione peroxidase, catalase, glutathione S-transferase and reduced glutathione levels were also decreased while testicular malondialdehyde level was increased after cadmium injection. On the other hand, serum luteinizing hormone, follicle stimulating hormone, sex hormone binding globulin and γ-glutamyl transpeptidase were increased after cadmium exposure. Cadmium also induced sperms loss. Co-administration of pectin with cadmium restores all the above parameters and sperms to the normal levels where pectin at higher dose was more effective than lower one. These results were supported by histochemical investigations. In conclusion, pectin can counteract the testicular toxicity and oxidative stress induced by cadmium and the effect was dose-dependent.


Asunto(s)
Antioxidantes/uso terapéutico , Cadmio/toxicidad , Contaminantes Ambientales/toxicidad , Estrés Oxidativo/efectos de los fármacos , Pectinas/uso terapéutico , Enfermedades Testiculares/prevención & control , Testículo/efectos de los fármacos , Animales , Antioxidantes/administración & dosificación , Antioxidantes/metabolismo , Cadmio/farmacocinética , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Contaminantes Ambientales/farmacocinética , Hormonas Esteroides Gonadales/metabolismo , Antígeno Ki-67/metabolismo , Masculino , Pectinas/administración & dosificación , Ratas , Ratas Wistar , Espermatogénesis/efectos de los fármacos , Enfermedades Testiculares/inducido químicamente , Enfermedades Testiculares/metabolismo , Enfermedades Testiculares/patología , Testículo/enzimología , Testículo/metabolismo , Testículo/patología , Distribución Tisular
11.
J Obstet Gynaecol ; 32(8): 756-9, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23075349

RESUMEN

This study comprised 74 infertile patients with familial Mediterranean fever (FMF), among which 26 women became pregnant. Pregnancies were followed according to the standard antenatal follow-up protocol of high-risk pregnancies. The principal outcome measures were the termination of pregnancy and its upshot. This study comprised 74 infertile patients with FMF. Of the cases, 12 (16.22%) had antiphospholipid syndrome (APS); 16 patients (21.62%) had a history of previous abdominal/pelvic surgery, which might have been contributing to delay of conception; 66 patients (89.18%) were on drug therapy by corticosteroids, colchicines and other agents. A total of 10/22 patients were delivered by caesarean section for complicated pregnancies. Six of the newborns were positive for the MEFV gene. Favourable pregnancy outcome occurs in patients with FMF treated with colchicine before and after pregnancy. Neonatal outcome was similar to that expected in the general population.


Asunto(s)
Colchicina/uso terapéutico , Fiebre Mediterránea Familiar , Resultado del Embarazo , Adolescente , Adulto , Fiebre Mediterránea Familiar/complicaciones , Fiebre Mediterránea Familiar/tratamiento farmacológico , Fiebre Mediterránea Familiar/genética , Femenino , Humanos , Recién Nacido , Infertilidad Femenina/etiología , Embarazo , Complicaciones del Embarazo/tratamiento farmacológico , Adulto Joven
12.
Sci Rep ; 11(1): 1986, 2021 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-33479284

RESUMEN

In this work, a fully integrated active microfluidic device transforming a conventional 96-well kit into point-of-care testing (POCT) device was implemented to improve the performance of traditional enzyme-linked immunosorbent assay (ELISA). ELISA test by the conventional method often requires the collection of 96 samples for its operation as well as longer incubation time from hours to overnight, whereas our proposed device conducts ELISA immediately individualizing a 96-well for individual patients. To do that, a programmable and disposable on-chip pump and valve were integrated on the device for precise control and actuation of microfluidic reagents, which regulated a reaction time and reagent volume to support the optimized protocols of ELISA. Due to the on-chip pump and valve, ELISA could be executed with reduced consumption of reagents and shortening the assay time, which are crucial for conventional ELISA using 96-well microplate. To demonstrate highly sensitive detection and easy-to-use operation, this unconventional device was successfully applied for the quantification of cardiac troponin I (cTnI) of 4.88 pg/mL using a minimum sample volume of 30 µL with a shorter assay time of 15 min for each ELISA step. The limit of detection (LOD) thus obtained was significantly improved than the conventional 96-well platform.

13.
Haematologica ; 95(12): 1996-2004, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20823133

RESUMEN

BACKGROUND: Exposure to γ-radiation causes rapid hematopoietic cell apoptosis and bone marrow suppression. However, there are no approved radiation countermeasures for the acute radiation syndrome. In this study, we demonstrated that natural δ-tocotrienol, one of the isomers of vitamin E, significantly enhanced survival in total body lethally irradiated mice. We explored the effects and mechanisms of δ-tocotrienol on hematopoietic progenitor cell survival after γ-irradiation in both in vivo and in vitro experiments. DESIGN AND METHODS: CD2F1 mice and human hematopoietic progenitor CD34(+) cells were treated with δ-tocotrienol or vehicle control 24 h before or 6 h after γ-irradiation. Effects of δ-tocotrienol on hematopoietic progenitor cell survival and regeneration were evaluated by clonogenicity studies, flow cytometry, and bone marrow histochemical staining. δ-tocotrienol and γ-irradiation-induced signal regulatory activities were assessed by immunofluorescence staining, immunoblotting and short-interfering RNA assay. RESULTS: δ-tocotrienol displayed significant radioprotective effects. A single injection of δ-tocotrienol protected 100% of CD2F1 mice from total body irradiation-induced death as measured by 30-day post-irradiation survival. δ-tocotrienol increased cell survival, and regeneration of hematopoietic microfoci and lineage(-)/Sca-1(+)/ckit(+) stem and progenitor cells in irradiated mouse bone marrow, and protected human CD34(+) cells from radiation-induced damage. δ-tocotrienol activated extracellular signal-related kinase 1/2 phosphorylation and significantly inhibited formation of DNA-damage marker γ-H2AX foci. In addition, δ-tocotrienol up-regulated mammalian target of rapamycin and phosphorylation of its downstream effector 4EBP-1. These alterations were associated with activation of mRNA translation regulator eIF4E and ribosomal protein S6, which is responsible for cell survival and growth. Inhibition of extracellular signal-related kinase 1/2 expression by short interfering RNA abrogated δ-tocotrienol-induced mammalian target of rapamycin phosphorylation and clonogenicity, and increased γ-H2AX foci formation in irradiated CD34(+) cells. CONCLUSIONS: Our data indicate that δ-tocotrienol protects mouse bone marrow and human CD34(+) cells from radiation-induced damage through extracellular signal-related kinase activation-associated mammalian target of rapamycin survival pathways.


Asunto(s)
Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Células Madre Hematopoyéticas/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Vitamina E/análogos & derivados , Animales , Antígenos CD34/metabolismo , Western Blotting , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Células de la Médula Ósea/efectos de la radiación , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/efectos de la radiación , Células Cultivadas , Relación Dosis-Respuesta en la Radiación , Activación Enzimática/efectos de los fármacos , Activación Enzimática/efectos de la radiación , Factor 4E Eucariótico de Iniciación/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/genética , Rayos gamma , Células Madre Hematopoyéticas/metabolismo , Células Madre Hematopoyéticas/efectos de la radiación , Histonas/metabolismo , Humanos , Masculino , Ratones , Microscopía Fluorescente , Fosforilación/efectos de los fármacos , Fosforilación/efectos de la radiación , Interferencia de ARN , Proteína S6 Ribosómica/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/efectos de la radiación , Análisis de Supervivencia , Serina-Treonina Quinasas TOR/genética , Vitamina E/farmacología
14.
Pharm Biol ; 48(5): 534-8, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20645796

RESUMEN

Chemical investigations from a foliar extract of Araucaria excelsa (Lamb.) (Araucariaceae) resulted in the identification of seven phenolic metabolites including one flavananol, one flavananol 3-O-glycoside, four C-glycoside flavonoids, and one phenolic acid. Structures were elucidated by spectral determination including: UV, NMR and MS analysis. Moderate antioxidant activity was observed with a 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay in comparison with the reference antioxidant ascorbic acid.


Asunto(s)
Antioxidantes/química , Antioxidantes/aislamiento & purificación , Pinus , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta , Flavonoides/química , Flavonoides/aislamiento & purificación , Fenoles/química , Fenoles/aislamiento & purificación , Polifenoles
15.
Sci Prog ; 103(2): 36850420922773, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32519922

RESUMEN

Seasonal variations in the temperatures of the hemispheres induce seasonal energy cycles between the hemispheres that drive tropical cyclones. Because the northern hemisphere has warmed more than the southern hemisphere, climate energy cycles develop between the hemispheres as well. The seasonal and climate energy cycles appear to interact among themselves, and tropical cyclone counts are affected by these interactions. Furthermore, the total number of tropical cyclones appears to have an increasing trend. The annual energy of tropical cyclones is nearly 1.46 × 1022 J yr-1, and climate cycle energy is between 4.0 and 6.6 × 1021 J per cycle. The magnitude of the climate energy cycles is thus large enough to alter the energy and frequency of the tropical cyclones. Given that the climate is changing, the energy and frequency of tropical cyclones may be changing as well. The subject is broad and this work is limited to parameterization of the physics of energy oscillations between the hemispheres, demonstrating the existence of climate energy cycles, and revealing interactions between climate and seasonal energy cycles. Also, this parameterization may assist researchers in obtaining more and coordinated data relative to these cycles.

16.
J Spec Oper Med ; 20(4): 100-103, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33320321

RESUMEN

The coronavirus disease 2019 (COVID-19) pandemic has demonstrated that new and devastating respiratory pathogens can emerge without warning. It is therefore imperative that Special Operations medical personnel be aware of the presence of emerging pathogens within their area of operation. Human bocavirus (HBoV) is a newly described member of a family of viruses known as the Parvovirinae that are often associated with acute respiratory illness. The presence of HBoV in the country of Georgia has not been previously reported. Nasal and throat swabs were collected from 95 symptomatic members of the Georgian military. HBoV was detected in 11 of them (12%). To our knowledge, this is the first report of HBoV infection in the country of Georgia. This finding may have a significant impact on members of the Special Operations community who train in Georgia as more data concerning the transmission, pathogenesis, and treatment of HBoV are accumulated and the role of HBoV in human disease is more clearly defined.


Asunto(s)
COVID-19 , Personal Militar , Humanos , Bocavirus Humano , Pandemias , SARS-CoV-2 , Georgia (República)
17.
Cell Rep ; 29(7): 1923-1933.e3, 2019 11 12.
Artículo en Inglés | MEDLINE | ID: mdl-31722207

RESUMEN

Myxovirus resistance 2 (MX2/MXB) is an interferon (IFN)-induced HIV-1 restriction factor that inhibits viral nuclear DNA accumulation. The amino-terminal domain of MX2 binds the viral capsid and is essential for inhibition. Using in vitro assembled Capsid-Nucleocapsid (CANC) complexes as a surrogate for the HIV-1 capsid lattice, we reveal that the GTPase (G) domain of MX2 contains a second, independent capsid-binding site. The importance of this interaction was addressed in competition assays using the naturally occurring non-antiviral short isoform of MX2 that lacks the amino-terminal 25 amino acids. Specifically, these experiments show that the G domain enhances MX2 function, and the foreshortened isoform acts as a functional suppressor of the full-length protein in a G-domain-dependent manner. The interaction of MX2 with its HIV-1 capsid substrate is therefore multi-faceted: there are dual points of contact that, together with protein oligomerization, contribute to the complexity of MX2 regulation.


Asunto(s)
Cápside/metabolismo , Infecciones por VIH/metabolismo , VIH-1/metabolismo , Proteínas de Resistencia a Mixovirus/metabolismo , Infecciones por VIH/genética , VIH-1/genética , Células HeLa , Humanos , Proteínas de Resistencia a Mixovirus/genética , Unión Proteica , Dominios Proteicos , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo
18.
Artículo en Inglés | MEDLINE | ID: mdl-31038056

RESUMEN

BACKGROUND: Diabetes Mellitus (DM) is a multisystemic disease involving the homeostasis of insulin secretion by the pancreatic islet beta cells (ß-cells). It is associated with hypertension, renal disease, and arterial and arteriolar vascular diseases. DISCUSSION: The classification of diabetes is identified as type 1 (gene linked ß-cell destruction in childhood) and type 2 (late onset associated with ß-cell overload and insulin resistance in peripheral tissues. Type 1 diabetes is characterized by insulin deficiency, type 2 diabetes by both insulin deficiency and insulin resistance. The former is a genetically programmed loss of insulin secretion whereas the latter constitutes a disruption of the homeostatic relationship between the opposing activity of ß- cell insulin and alpha cell (α-cell) glucagon of the Islets of Langerhans. The condition could also occur in pregnancy, as a prenatal occurring event, possibly triggered by the hormonal changes of pregnancy combined with ß-cell overload. This review discusses the molecular basis of the biomolecular changes that occur with respect to glucose homeostasis and related diseases in DM. The underlying link between pancreatic, renal, and microvascular diseases in DM is based on oxidative stress and the Unfolded Protein Response (UPR). CONCLUSION: Studying proteome changes in diabetes can deepen our understanding of the biomolecular basis of disease and help us acquire more efficient therapies.


Asunto(s)
Desarrollo Infantil/fisiología , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Proteoma/metabolismo , Animales , Niño , Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Humanos , Células Secretoras de Insulina/metabolismo , Islotes Pancreáticos/metabolismo , Proteoma/genética
20.
J Comput Biol ; 14(2): 131-43, 2007 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-17456012

RESUMEN

In this paper, we study the problem of computing the similarity of two protein structures by measuring their contact-map overlap. Contact-map overlap abstracts the problem of computing the similarity of two polygonal chains as a graph-theoretic problem. In R3, we present the first polynomial time algorithm with any guarantee on the approximation ratio for the 3-dimensional problem. More precisely, we give an algorithm for the contact-map overlap problem with an approximation ratio of sigma where sigma = min{sigma(P1), sigma(P2)} 0, is hard.


Asunto(s)
Algoritmos , Biología Computacional/métodos , Proteínas/química , Modelos Químicos , Proteínas/metabolismo
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