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1.
Org Chem Front ; 11(3): 843-853, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38298564

RESUMO

A series of six azaborahelicenes with varying electron-donor substitution at the 4-position of the aryl residue (i.e., naphthyl) or with variable π-extension of the aryl residue (thianthrenyl, anthryl, pyrenyl) was prepared with an efficient and flexible synthetic protocol. These different types of functionalization afforded notably pronounced intramolecular charge-transfer (ICT) character for the dyes with the strongest electron donor substitution (NMe2) or easiest to oxidize aryl residues, as evidenced by photophysical investigations. These effects also impact the corresponding chiroptical properties of the separated M- and P-enantiomers, which notably display circularly polarized luminescence (CPL) with dissymmetry factors in the order of magnitude of 10-4 to 10-3. Theoretical calculations confirm the optical spectroscopy data and are in agreement with the proposed involvement of ICT processes.

2.
IEEE Trans Biomed Circuits Syst ; 16(6): 1030-1043, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36191107

RESUMO

This work reports the first CMOS molecular electronics chip. It is configured as a biosensor, where the primary sensing element is a single molecule "molecular wire" consisting of a ∼100 GΩ, 25 nm long alpha-helical peptide integrated into a current monitoring circuit. The engineered peptide contains a central conjugation site for attachment of various probe molecules, such as DNA, proteins, enzymes, or antibodies, which program the biosensor to detect interactions with a specific target molecule. The current through the molecular wire under a dc applied voltage is monitored with millisecond temporal resolution. The detected signals are millisecond-scale, picoampere current pulses generated by each transient probe-target molecular interaction. Implemented in a 0.18 µm CMOS technology, 16k sensors are arrayed with a 20 µm pitch and read out at a 1 kHz frame rate. The resulting biosensor chip provides direct, real-time observation of the single-molecule interaction kinetics, unlike classical biosensors that measure ensemble averages of such events. This molecular electronics chip provides a platform for putting molecular biosensing "on-chip" to bring the power of semiconductor chips to diverse applications in biological research, diagnostics, sequencing, proteomics, drug discovery, and environmental monitoring.


Assuntos
Técnicas Biossensoriais , Eletrônica , Análise de Sequência com Séries de Oligonucleotídeos , Semicondutores , DNA/química , Nanotecnologia , Técnicas Biossensoriais/métodos
3.
Biomedicines ; 10(2)2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35203665

RESUMO

INTRODUCTION: Polycystic ovary syndrome (PCOS) is an endocrinological disorder that affects 5-15% of women of their reproductive age and is a frequent cause of infertility. Major symptoms include hyperandrogenism, ovulatory dysfunction, and often obesity and/or insulin resistance. PCOS also represents a state of chronic low-grade inflammation that is closely interlinked with the metabolic features. "Classical" pro-inflammatory lipid mediators such as prostaglandins (PG), leukotrienes (LT), or thromboxanes (TX) are derived from arachidonic acid (AA) and are crucial for the initial response. Resolution processes are driven by four families of so-called specialized pro-resolving mediators (SPMs): resolvins, maresins, lipoxins, and protectins. The study aimed to establish lipid mediator profiles of PCOS patients compared to healthy women to identify differences in their resolutive and pro-inflammatory lipid parameters. MATERIAL AND METHODS: Fifteen female patients (18-45 years) were diagnosed with PCOS according to Rotterdam criteria, and five healthy women, as a comparator group, were recruited for the study. The main outcome measures were: pro-inflammatory lipid mediators (PG, LT, TX) and their precursor AA, SPMs (resolvins, maresins, protectins, lipoxins), their precursors EPA, DHA, DPA, and their active biosynthesis pathway intermediates (18-HEPE, 17-HDHA, 14-HDHA). RESULTS: The level of pro-inflammatory parameters in serum was significantly higher in PCOS-affected women. The ratio (sum of pro-inflammatory molecules)/(sum of SPMs plus hydroxylated intermediates) reflecting the inflammatory state was significantly lower in the group of healthy women. CONCLUSION: There is a strong pro-inflammatory state in PCOS patients. Further research will clarify whether supplementation with SPMs or their precursors may improve this state.

4.
Med Hypotheses ; 145: 110340, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33069094

RESUMO

COVID-19 is a new disease caused by coronavirus SARS-CoV-2. It was first described in 2019, developed into an epidemic in January 2020 and has spread the global to the present COVID-19 pandemic. Specialized pro­resolving mediators (SPMs) may play a new role in the management of this lung disease because SPM actively stimulate the resolution of infectious inflammation and are organ protective in animal disease models. Many tissues have been suitable targets for treating inflammation with SPMs or their active precursors 18-HEPE, 17-HDHA and the 14-HDHA, in order to elicit dynamic resolution of inflammation. Here we discuss the possible mode of action of these substances in the management of SARS Covid 19.


Assuntos
COVID-19/imunologia , COVID-19/terapia , Ácidos Graxos Ômega-3/química , Mediadores da Inflamação/metabolismo , Inflamação/metabolismo , Lipídeos/química , Animais , Humanos , Modelos Teóricos
5.
Int J Mol Sci ; 22(1)2020 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-33396555

RESUMO

PCOS as the most common endocrine disorder of women in their reproductive age affects between 5-15 % of the female population. Apart from its cardinal symptoms, like irregular and anovulatory cycles, hyperandrogenemia and a typical ultrasound feature of the ovary, obesity, and insulin resistance are often associated with the disease. Furthermore, PCOS represents a status of chronic inflammation with permanently elevated levels of inflammatory markers including IL-6 and IL-18, TNF-α, and CRP. Inflammation, as discovered only recently, consists of two processes occurring concomitantly: active initiation, involving "classical" mediators including prostaglandins and leukotrienes, and active resolution processes based on the action of so-called specialized pro-resolving mediators (SPMs). These novel lipid mediator molecules derive from the essential ω3-poly-unsaturated fatty acids (PUFAs) DHA and EPA and are synthesized via specific intermediates. The role and benefits of SPMs in chronic inflammatory diseases like obesity, atherosclerosis, and Diabetes mellitus has become a subject of intense research during the last years and since PCOS features several of these pathologies, this review aims at summarizing potential roles of SPMs in this disease and their putative use as novel therapeutics.


Assuntos
Ácidos Docosa-Hexaenoicos/farmacologia , Inflamação/prevenção & controle , Síndrome do Ovário Policístico/complicações , Animais , Feminino , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia
6.
Org Lett ; 21(19): 8080-8084, 2019 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-31545060

RESUMO

The syntheses of linoleic acid esters of hydroxy linoleic acids (LAHLAs) present in oat oil and human serum have been achieved, providing access to material for testing and the determination of the stereochemistry of the natural compounds. While 9- and 13-LAHLAs were found to be a mixture of enantiomers 15-LAHLA is generated in a single optical form in oat oil. The stereochemistry of 15-LAHLA in oat oil was found to be opposite to that reported for digalactosyldiacylglycerol that possesses an embedded 15-LAHLA.

8.
Nat Biotechnol ; 21(4): 387-91, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12627168

RESUMO

Vascular leak syndrome is a major and often dose-limiting side effect of immunotoxins and cytokines. We postulated that this syndrome is initiated by damage to vascular endothelial cells. Our earlier studies identified a three-amino acid motif that is shared by toxins, ribosome-inactivating proteins, and interleukin-2, all of which cause this problem. We have now generated a panel of recombinant ricin A chains with mutations in this sequence or in amino acids flanking it in the three-dimensional structure. These have been evaluated alone and as immunotoxins for activity, ability to induce pulmonary vascular leak in mice, pharmacokinetics, and activity in tumor-xenografted mice. One mutant was comparable to the ricin A chain used before in all respects except that it did not cause vascular leak at the same dose and, when used as an immunotoxin, was more effective in xenografted SCID mice.


Assuntos
Síndrome de Vazamento Capilar/tratamento farmacológico , Endotélio/efeitos dos fármacos , Engenharia Genética/métodos , Imunotoxinas/genética , Ricina/administração & dosagem , Motivos de Aminoácidos , Animais , Síndrome de Vazamento Capilar/induzido quimicamente , Imunotoxinas/administração & dosagem , Imunotoxinas/metabolismo , Imunotoxinas/toxicidade , Dose Letal Mediana , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Linfoma/tratamento farmacológico , Camundongos , Camundongos SCID , Mutagênese Sítio-Dirigida , Engenharia de Proteínas/métodos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Ricina/genética , Ricina/metabolismo , Ricina/toxicidade
9.
Rev. mex. radiol ; 52(4): 153-6, oct.-dic. 1998. tab
Artigo em Espanhol | LILACS | ID: lil-241367

RESUMO

Se presenta la experiencia obtenida en cinco años en el Servicio de Radiología del Hospital General "Dr. Manuel Gea González" en relación al manejo invasivo de los abscesos abdominales por drenaje percutáneo guiado por ultrasonido. Se trataron 244 pacientes con diferentes colecciones intrabdominales, a quienes se realizó drenaje por esta vía. Se drenaron 197 abscesos hepáticos amibianos, dos abscesos piógenos, dos abscesos micóticos, 10 abscesos residuales postquirúrgicos, tres abscesos perirrenales, 14 quistes renales, ocho quistes hepáticos, dos hematomas perirrenales espontáneos, dos pseudoquistes de páncreas infectados y cuatro hematomas de lecho vesicular. Se obtuvo éxito en el 97.95 por ciento de los enfermos; las complicaciones fueron mínimas


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Terapia por Ultrassom , Drenagem , Drenagem/instrumentação , Abscesso Abdominal/terapia , Abscesso Abdominal , Sucção/instrumentação
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