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1.
Apoptosis ; 29(7-8): 1019-1037, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38615304

RESUMEN

Ferroptosis is a new discovered regulated cell death triggered by the ferrous ion (Fe2+)-dependent accumulation of lipid peroxides associated with cancer and many other diseases. The mechanism of ferroptosis includes oxidation systems (such as enzymatic oxidation and free radical oxidation) and antioxidant systems (such as GSH/GPX4, CoQ10/FSP1, BH4/GCH1 and VKORC1L1/VK). Among them, ferroptosis suppressor protein 1 (FSP1), as a crucial regulatory factor in the antioxidant system, has shown a crucial role in ferroptosis. FSP1 has been well validated to ferroptosis in three ways, and a variety of intracellular factors and drug molecules can alleviate ferroptosis via FSP1, which has been demonstrated to alter the sensitivity and effectiveness of cancer therapies, including chemotherapy, radiotherapy, targeted therapy and immunotherapy. This review aims to provide important frameworks that, bring the regulation of FSP1 mediated ferroptosis into cancer therapies on the basis of existing studies.


Asunto(s)
Ferroptosis , Neoplasias , Ferroptosis/efectos de los fármacos , Ferroptosis/genética , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/genética , Neoplasias/patología , Animales , Proteína de Unión al Calcio S100A4/metabolismo , Proteína de Unión al Calcio S100A4/genética
2.
Eur Neurol ; 87(2): 93-104, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38657568

RESUMEN

INTRODUCTION: Dementia is a neurodegenerative disease with insidious onset and progressive progression, of which the most common type is Alzheimer's disease (AD). Lithium, a trace element in the body, has neuroprotective properties. However, whether lithium can treat dementia or AD remains a highly controversial topic. Therefore, we conducted a meta-analysis. METHODS: A systematic literature review was conducted on PubMed, Embase, and Web of Science. Comparison of the effects of lithium on AD or dementia in terms of use, duration, and dosage, and meta-analysis to test whether lithium therapy is beneficial in ameliorating the onset of dementia or AD. Sensitivity analyses were performed using a stepwise exclusion method. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of included studies. We determined the relative risk (RR) between patient groups using a random-effects model. RESULTS: A total of seven studies were included. The forest plot results showed that taking lithium therapy reduced the risk of AD (RR 0.59, 95% confidence interval [CI]: 0.44-0.78) and is also protective in reducing the risk of dementia (RR 0.66, 95% CI: 0.56-0.77). The duration of lithium therapy was able to affect dementia incidence (RR 0.70, 95% CI: 0.55-0.88); however, it is unclear how this effect might manifest in AD. It is also uncertain how many prescriptions for lithium treatment lower the chance of dementia development. CONCLUSION: The duration of treatment and the usage of lithium therapy seem to lower the risk of AD and postpone the onset of dementia.


Asunto(s)
Enfermedad de Alzheimer , Demencia , Humanos , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/epidemiología , Demencia/epidemiología , Demencia/tratamiento farmacológico , Compuestos de Litio/uso terapéutico , Prevalencia , Litio/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico
3.
Opt Express ; 31(11): 17861-17877, 2023 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-37381509

RESUMEN

In large-scale water quality evaluation, traditional field-measured data lack spatial-temporal representativeness, and the role of conventional remote sensing parameters (SST, Chla, TSM, etc.) is controversial. By calculating and grading the hue angle of a water body, a Forel-Ule index (FUI) can be obtained, which provides a comprehensive statement of water condition. Using MODIS imagery, hue angles are extracted with better accuracy than the literature's method. It is found that FUI changes in the Bohai Sea have correlated consistently with water quality. The decreasing trend of non-excellent water quality areas in the Bohai Sea was highly correlated with FUI (R2 = 0.701) during the government-dominated land-based pollution reduction program (2012-2021). FUI can monitor and evaluate seawater quality.

4.
J Phys Chem A ; 127(3): 799-816, 2023 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-36648878

RESUMEN

Recent high-level theoretical calculations predict a mild temperature dependence for HO2 + HO2 inconsistent with state-of-the-art experimental determinations that upheld the stronger temperature dependence observed in early experiments. Via MultiScale Informatics analysis of the theoretical and experimental data, we identified an alternative interpretation of the raw experimental data that uses HO2 + HO2 rate constants nearly identical to theoretical predictions─implying that the theoretical and experimental data are actually consistent, at least when considering the raw data from experimental studies. Similar analyses of typical signals from low-temperature experiments indicate that an HOOOOH intermediate─identified by recent theory but absent from earlier interpretations─yields modest effects that are smaller than, but may have contributed to, the scatter in data among different experiments. More generally, the findings demonstrate that modern chemical theories and experiments have progressed to a point where meaningful comparison requires joint consideration of their data simultaneously.

5.
Faraday Discuss ; 238(0): 355-379, 2022 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-35866720

RESUMEN

In 1922, Lindemann proposed the now-well-known mechanism for pressure-dependent rate constants for unimolecular reactions: reactant molecules with sufficiently high energies dissociate more quickly than collisions can reestablish the Boltzmann distribution of the internal energies of the molecule during its dissociation at low pressures - yielding pressure-dependent rate constants for unimolecular reactions due to the preferential depletion of the high energy states capable of dissociation. In the last century, incredible progress has been made in achieving a far greater understanding of and quantitative predictions for unimolecular and association reactions. In the modern era, pressure-dependent phenomenological rate constants are now nearly universally used to describe the rates of unimolecular and associative reactions in phenomenological kinetic modeling. However, there is a second, more indirect, implication of Lindemann's mechanism that relates to how these dissociation-induced non-equilibrium distributions impact bimolecular reactions, including non-associative bimolecular reactions - which are generally not considered to have pressure-dependent rate constants. Yet, as we show herein, the same high energy states depleted due to dissociation would otherwise react most rapidly in high-activation-energy bimolecular reactions - yielding a mechanism for pressure-dependent rate constants for bimolecular reactions (including non-associative reactions). Here, we present results from a case study for CH2O dissociation, isomerization, and bimolecular reaction with O2 to explore this question. Results from our master equation calculations indicate that the effect of dissociation-induced non-equilibrium distributions on bimolecular reactions can be substantial - even when chemical timescales are well separated from internal energy relaxational timescales (i.e. when the traditional rate constant description would be thought to apply). This effect is found to be more pronounced - and more complex - for bimolecular reactions involving molecular entities whose chemical timescales are merged with the internal energy relaxational timescales. Finally, we present some ideas for discussion regarding what should be considered as "chemical species" in phenomenological kinetic models.

6.
J Phys Chem A ; 126(44): 8305-8314, 2022 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-36300359

RESUMEN

The multi-structural approximation with torsional anharmonicity (MS-T) method and its variants have been widely used for calculating conformational-rovibrational partition functions of large molecules. The present work aimed to propose a systematic method to assess and explain the performance of various variants of the MS-T method. First, we proposed the simplest variant MS-T(2NN) (two nearest neighborhood torsions are coupled) and systematically validated it for large alkanes n-CnH2n+2 (n = 6-10) and their transition states of hydrogen abstraction reactions. Second, we proposed a metric-based method to explain the underlying reason for the good performance of MS-T(2NN)─it includes the torsional conformers that have dominant contributions to the partition function calculations. These conformers are closer to the lowest-energy conformer in the space of dihedral and energy metrics. Third, the same observation and explanation apply to the other two variants, MS-2DT (any two torsions are coupled) and MS-3DT (any three torsional are coupled), which contain increasingly more torsional conformers than MS-T(2NN) but are subsets of the complete set of torsional conformers considered by the MS-T method. Overall, the present method provides a mathematically rigorous and computationally effective diagnosis tool to assess various MS-T methods dealing with the torsional anharmonicity of large molecules in the partition function calculation.


Asunto(s)
Hidrógeno , Termodinámica , Conformación Molecular , Hidrógeno/química
7.
Mol Carcinog ; 59(6): 575-589, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32187756

RESUMEN

Dihydromethysticin (DHM), a natural compound derived from Kava, has been reported to be effective against mental disorders and some malignant tumors. However, little is known about the inhibitory effect of DHM on colorectal cancer (CRC). First, we examined the impact of DHM on human colon cancer cell lines, which demonstrated that DHM inhibits proliferation, migration, and invasion and promotes apoptosis and cell cycle arrest in colon cancer cells in vitro. Using small hairpin RNA, we inhibited nucleotide-oligomerization domain-like receptor subfamily C3 (NLRC3)/phosphoinositide 3-kinase (PI3K) pathway to elucidate the partial signaling of DHM-mediated tumor suppression. Additionally, using an ectopic human CRC model, we verified whether DHM inhibits tumor growth and angiogenesis via the NLRC3/PI3K pathway in vivo. Overall, DHM showed an inhibitory effect on CRC by altering cell proliferation, migration, invasion, apoptosis, cell cycle, and angiogenesis, possibly via the NLRC3/PI3K pathway. Thus, DHM may be a promising candidate for CRC therapy.


Asunto(s)
Neoplasias Colorrectales/tratamiento farmacológico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Kava/química , Fosfatidilinositol 3-Quinasas/metabolismo , Pironas/farmacología , Animales , Apoptosis , Ciclo Celular , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Invasividad Neoplásica , Fosfatidilinositol 3-Quinasas/genética , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
8.
J Phys Chem A ; 124(42): 8643-8652, 2020 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-32986416

RESUMEN

An ab initio chemical kinetics study of the reactions of methyl butanoate (MB) with hydroperoxyl radical (HO2) is presented in this paper. Particular interest is placed on determining the influences of torsional anharmonicity and addition reaction on the rate constants of hydrogen abstraction reactions. Stationary points on the potential energy surface of MB + HO2 are calculated at the level of QCISD(T)/CBS//B3LYP/6-311++G(d,p). The transition state theory (TST) is used to calculate the high-pressure limit rate constants of the hydrogen abstraction reactions over a board range of temperature (500-2000 K). Anharmonicity of low-frequency torsional modes is considered in the rate calculations by using the one-dimensional hindered rotor approximation and the internal-coordinate multistructural approximation; the latter is used as a higher-level theoretical method to examine the applicability of the former in dealing with strongly coupled torsional modes. The calculated rate constants are compared with the available data from the literature and observed discrepancies are analyzed in detail. An energetically lowest-lying addition reaction with subsequent isomerization and decomposition reactions are identified on the potential energy surface. The multiple-well Master equation analysis shows that these reactions have a secondary influence on the rate constants in the temperature range of interest.

9.
Acta Biochim Biophys Sin (Shanghai) ; 52(11): 1247-1256, 2020 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-33166992

RESUMEN

Intrahepatic cholangiocarcinoma (ICC) arises from cholangiocytes in the intrahepatic bile duct and is the second most common type of liver cancer. The overexpression of COUP-TFII has been observed in several types of malignancies. However, its role in ICC progression remains unclear. In this study, we found that the protein level of COUP-TFII was increased, but the mRNA level was unchanged in ICC tissues. High protein expression was positively associated with tumor size, lymph node metastasis, and poor prognosis in ICC patients. Furthermore, the overexpression of COUP-TFII promoted the proliferation, migration, and invasion of ICC cells in vitro and enhanced tumor growth and metastasis in nude mouse models. Mechanistic studies revealed that COUP-TFII induced epithelial-to-mesenchymal transition in ICC cells by upregulating Snail expression. Moreover, the activation of PI3K/AKT signaling led to the upregulation of COUP-TFII protein expression in ICC. Together, these findings indicate that COUP-TFII promotes epithelial-to-mesenchymal transition and metastasis in ICC and suggest that this protein is a potential target for adjuvant therapy for these patients.


Asunto(s)
Neoplasias de los Conductos Biliares/genética , Factor de Transcripción COUP II/genética , Factor de Transcripción COUP II/metabolismo , Colangiocarcinoma/genética , Transición Epitelial-Mesenquimal/genética , Factores de Transcripción de la Familia Snail/genética , Anciano , Animales , Neoplasias de los Conductos Biliares/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/patología , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Metástasis de la Neoplasia/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Pronóstico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factores de Transcripción de la Familia Snail/metabolismo , Regulación hacia Arriba
10.
Phys Chem Chem Phys ; 21(9): 5232-5242, 2019 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-30775733

RESUMEN

The isomerization and dissociation reactions of methyl decanoate (MD) radicals were theoretically investigated by using high-level theoretical calculations based on a two-layer ONIOM method, employing the QCISD(T)/CBS method for the high layer and the M06-2X/6-311++G(d,p) method for the low layer. Temperature- and pressure-dependent rate coefficients for the involved reactions were computed by using the transition state theory and the Rice-Ramsperger-Kassel-Marcus/Master-equation method. The structure-reactivity relationships were explored for the complicated multiple-well interconnected system of ten isomeric MD radicals. Comparative studies of methyl butanoate (MB) and MD were also performed systematically. Results show that the isomerization reactions are appreciably responsible for the population distribution of MD radicals at low and intermediate temperatures, while the ß-scission reactions are dominant at higher temperatures. Although the rate constants of MB specific to methyl esters are close to those of MD in certain temperature ranges, MB is unable to simulate most of the dissociation reactions due to its short aliphatic chain. Significant differences of rate constants for isomerization reactions were observed between the calculated results and the literature data, which were estimated by analogy to alkane systems, but the rate constants of ß-scissions show generally good agreement between theory and experiment. The current work extends kinetic data for isomerization and dissociation reactions of MD radicals, and it serves as a reference for the studies of detailed combustion chemistry of practical biodiesels.

11.
J Phys Chem A ; 123(1): 103-110, 2019 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-30501195

RESUMEN

The thermal decomposition of furfural is investigated in a flow tube reactor at 30 Torr by synchrotron vacuum ultraviolet photoionization mass spectrometry (SVUV-PIMS) at temperatures from 1023 to 1273 K. Over 20 kinds of pyrolysis products, including short-lived radicals, stable oxygen-containing compounds, and hydrocarbons, are identified from the scanning photoionization efficiency (PIE) spectra. Vinylketene (CH2═CH-CH═C═O), which has been shown to be an important primary product, is also directly observed. The possible steps of hydrogen atom addition and hydrogen atom abstraction in the thermal decomposition of furfural are studied by theoretical calculations at the CBS-QB3 level. In addition to unimolecular decomposition, hydrogen atom addition followed by ring opening can lead to the production of vinylketene.

12.
J Phys Chem A ; 123(10): 1929-1936, 2019 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-30811197

RESUMEN

Criegee intermediates have raised much attention in atmospheric chemistry because of their significance in ozonolysis mechanism. The simplest Criegee intermediate, CH2OO, and its reactions with acrylic acid including cycloadditions and insertions as main entrance channels have been investigated at CCSD(T)/cc-pVTZ//M06-2X/6-31G(d,p) level. Temperature- and pressure-dependent kinetics were predicted by solving the time-dependent master equations based on Rice-Ramsperger-Kassel-Marcus theory using MESS program, with temperatures from 200 to 500 K and pressures from 0.001 to 1000 atm. Variational transition state theory (VTST) was used for barrierless pathways and conventional transition state theory (CTST) for pathways with distinct barriers. Results indicate that hydroperoxymethyl acrylate is the dominant product under atmospheric conditions. The combination of two reactants will reduce the volatility and makes a possible factor that induces formation of secondary organic aerosols, which suggests CH2OO's entangled role in ever-increasing air pollution.

13.
J Phys Chem A ; 122(21): 4882-4893, 2018 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-29745664

RESUMEN

A two-layer ONIOM[QCISD(T)/CBS:DFT] method was proposed for the high-level single-point energy calculations of large biodiesel molecules and was validated for the hydrogen abstraction reactions of unsaturated methyl esters that are important components of real biodiesel. The reactions under investigation include all the reactions on the potential energy surface of C nH2 n-1COOCH3 ( n = 2-5, 17) + H, including the hydrogen abstraction, the hydrogen addition, the isomerization (intramolecular hydrogen shift), and the ß-scission reactions. By virtue of the introduced concept of chemically active center, a unified specification of chemically active portion for the ONIOM (ONIOM = our own n-layered integrated molecular orbital and molecular mechanics) method was proposed to account for the additional influence of C═C double bond. The predicted energy barriers and heats of reaction by using the ONIOM method are in very good agreement with those obtained by using the widely accepted high-level QCISD(T)/CBS theory, as verified by the computational deviations being less than 0.15 kcal/mol, for almost all the reaction pathways under investigation. The method provides a computationally accurate and affordable approach to combustion chemists for high-level theoretical chemical kinetics of large biodiesel molecules.

14.
Clin Chem Lab Med ; 55(9): 1284-1290, 2017 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-28222013

RESUMEN

Background We aimed to evaluate the commutability of external quality assessment (EQA) materials, aqueous solutions, and commercial reference materials (calibrators and controls), and the accuracy of routine systems for serum triglyceride measurements. Methods According to the clinical and laboratory standards institute (CLSI) EP14-A3 protocol, we analyzed 43 fresh patient specimens and 32 processed materials including lyophilized samples, human serum pools, liquid reagents, swine sera and aqueous solutions by 14 routine methods (evaluated methods) and an isotope dilution liquid chromatography tandem mass spectrometry method (ID-LC/MS/MS) (comparative method). The accuracy of the routine method was evaluated by analyzing the absolute bias, relative bias, and the bias at three medical decision levels based on CLSI EP9-A3. Results Frozen serum samples and swine sera were commutable for all of the assays. The EQA/PT materials, commercial calibrators and control materials showed matrix effects differently on routine methods. The aqueous glycerol solutions were generally noncommutable for routine method. All except one routine analytical systems met the National Cholesterol Education Program (NCEP) recommended analytical performance guideline analytical quality criteria for total error. Conclusions Matrix effects and calibration biases existed in measurements of serum triglyceride. Continued efforts are needed to improve the accuracy and comparability of routine measurements.


Asunto(s)
Análisis Químico de la Sangre , Triglicéridos/sangre , Animales , Cromatografía Liquida , Humanos , Espectrometría de Masas en Tándem
15.
Clin Chem Lab Med ; 54(8): 1319-27, 2016 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-27010777

RESUMEN

BACKGROUND: In this study, we analyzed frozen sera with known commutabilities for standardization of serum electrolyte measurements in China. METHODS: Fresh frozen sera were sent to 187 clinical laboratories in China for measurement of four electrolytes (sodium, potassium, calcium, and magnesium). Target values were assigned by two reference laboratories. Precision (CV), trueness (bias), and accuracy [total error (TEa)] were used to evaluate measurement performance, and the tolerance limit derived from the biological variation was used as the evaluation criterion. RESULTS: About half of the laboratories used a homogeneous system (same manufacturer for instrument, reagent and calibrator) for calcium and magnesium measurement, and more than 80% of laboratories used a homogeneous system for sodium and potassium measurement. More laboratories met the tolerance limit of imprecision (coefficient of variation [CVa]) than the tolerance limits of trueness (biasa) and TEa. For sodium, calcium, and magnesium, the minimal performance criterion derived from biological variation was used, and the pass rates for total error were approximately equal to the bias (<50%). For potassium, the pass rates for CV and TE were more than 90%. Compared with the non homogeneous system, the homogeneous system was superior for all three quality specifications. CONCLUSIONS: The use of commutable proficiency testing/external quality assessment (PT/EQA) samples with values assigned by reference methods can monitor performance and provide reliable data for improving the performance of laboratory electrolyte measurement. The homogeneous systems were superior to the non homogeneous systems, whereas accuracy of assigned values of calibrators and assay stability remained challenges.


Asunto(s)
Técnicas de Laboratorio Clínico/normas , Electrólitos/sangre , Calcio/sangre , China , Humanos , Magnesio/sangre , Potasio/sangre , Sodio/sangre
16.
Clin Lab ; 62(5): 921-30, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27349020

RESUMEN

BACKGROUND: Measuring serum magnesium plays an important role in the diagnosis of diseases. The performance of serum magnesium measurements is most conveniently monitored by external quality assessment (EQA) or proficiency testing (PT) schemes. However, the commutability of EQA samples and calibrators is often unknown, and the effectiveness of EQA schemes is limited. We designed the present study to evaluate the matrix effects of processed materials and the accuracy of routine methods. METHODS: Inductively coupled plasma mass spectrometry was applied as a comparative method, and 12 routine methods composed of 12 kits, their supporting calibrators, and a Hitachi 7180 automatic analyzer were chosen as the test methods. Serum from 48 single patients and 24 processed materials were quantified by the comparative and routine methods. The 95% prediction intervals and relative bias were calculated at three medical decision levels (0.60 mmol/L, 1.00 mmol/L, and 2.50 mmol/L) according to EP9-A2 and EP14-A2. The commutability of the materials was evaluated by comparing the values of the processed materials with the limit bias, and the accuracy of the routine methods was evaluated by the relative bias. RESULTS: The precision of all of the assays was good (total CV < 2.01%), and the decision coefficients were high, most were greater than 0.99. The 2013 and 2014 EQA samples showed positive matrix effects in some of the assays; the human serum pools were commutable in all of the assays; the certified reference materials were commutable in most of the assays; the calibrators showed matrix effects in some of the assays; the aqueous reference materials showed matrix effects in most of the assays and could only be used in the reference methods. For all of the assays, the range of the mean bias was -0.04 - 0.06 mmol/L (-4.52% - 7.20%), and the range of the expected bias at the three medical decision levels was -0.03 - 0.06 mmol/L (-4.27% - 9.30%) at 0.6 mmol/L, -0.05 - 0.06 mmol/L (-4.79% - 6.31%) at 1.00 mmol/L, and -0.364 - 0.10 mmol/L (-13.66% - 4.05%) at 2.50 mmol/L. CONCLUSIONS: For most of the assays, the biases were in an acceptable range, whereas the accuracy of some of the assays needs improvement. Human serum pools prepared from patient samples were commutable, and other materials still exhibited matrix effects.


Asunto(s)
Sesgo , Técnicas de Laboratorio Clínico/normas , Magnesio/sangre , Calibración , Humanos , Estándares de Referencia
17.
Int J Clin Pract ; 70(12): 1019-1026, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28032425

RESUMEN

AIMS: The aim of this study was to identify and describe characteristics of women with heart failure (HF) and urinary incontinence (UI) who used absorbent products to manage UI and to explore the relationship between absorbent products use and women's perceptions about UI. METHODS: Secondary analyses were conducted on an existing dataset from a study of adults with HF. Descriptive statistics, univariate analyses, binary and multivariate logistic regression were used to identify factors and explore factors related to UI absorbent products use. Mediation analysis was also performed. RESULTS: One hundred women had UI and information about absorbent products use. One-third reported that their UI started before their HF diagnosis. Comorbidities were prevalent: hypertension (83%), diabetes mellitus (53%), probable depression (68%) and severe depression (42%). Eighty-two women reported using absorbent products. Women with severe UI (OR 0.220, 95% CI 0.052-0.925) and white women (OR 0.174, 95% CI 0.044-0.692) were more likely to use absorbent products when compared to women with less severe UI and women of colour. Use of absorbent products led to perceptions about the importance to get help for UI, which, in turn led to higher distress from UI. CONCLUSION: To provide interventions that reduce distress from UI in women already burdened with a serious chronic disease, clinicians must screen women who have HF for UI. Clinicians must also actively listen to how women manage UI, explore their perceptions about importance to get treatment, and understand their expectations for that treatment.


Asunto(s)
Almohadillas Absorbentes , Actitud Frente a la Salud , Depresión/psicología , Insuficiencia Cardíaca/complicaciones , Incontinencia Urinaria/complicaciones , Incontinencia Urinaria/prevención & control , Adulto , Anciano , Comorbilidad , Depresión/etiología , Femenino , Humanos , Modelos Logísticos , Persona de Mediana Edad , Percepción , Prevalencia , Incontinencia Urinaria/fisiopatología
18.
Proc Natl Acad Sci U S A ; 110(46): 18650-5, 2013 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-24127581

RESUMEN

DIM (3,3'-diindolylmethane), a small molecule compound, is a proposed cancer preventive agent that can be safely administered to humans in repeated doses. We report that administration of DIM in a multidose schedule protected rodents against lethal doses of total body irradiation up to 13 Gy, whether DIM dosing was initiated before or up to 24 h after radiation. Physiologic submicromolar concentrations of DIM protected cultured cells against radiation by a unique mechanism: DIM caused rapid activation of ataxia-telangiectasia mutated (ATM), a nuclear kinase that regulates responses to DNA damage (DDR) and oxidative stress. Subsequently, multiple ATM substrates were phosphorylated, suggesting that DIM induces an ATM-dependent DDR-like response, and DIM enhanced radiation-induced ATM signaling and NF-κB activation. DIM also caused activation of ATM in rodent tissues. Activation of ATM by DIM may be due, in part, to inhibition of protein phosphatase 2A, an upstream regulator of ATM. In contrast, DIM did not protect human breast cancer xenograft tumors against radiation under the conditions tested. In tumors, ATM was constitutively phosphorylated and was not further stimulated by radiation and/or DIM. Our findings suggest that DIM is a potent radioprotector and mitigator that functions by stimulating an ATM-driven DDR-like response and NF-κB survival signaling.


Asunto(s)
Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Activación Enzimática/efectos de los fármacos , Indoles/farmacología , Traumatismos Experimentales por Radiación/prevención & control , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Línea Celular , Ensayo Cometa , Femenino , Proteínas Fluorescentes Verdes , Inmunoprecipitación , Indoles/uso terapéutico , Estimación de Kaplan-Meier , Luciferasas , Ratones , Fosforilación/efectos de los fármacos , Proteína Fosfatasa 2/metabolismo , ARN Interferente Pequeño/genética , Traumatismos Experimentales por Radiación/tratamiento farmacológico , Radiación Ionizante , Ratas , Ratas Sprague-Dawley
19.
Reprod Biol ; 24(2): 100893, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38754347

RESUMEN

Metastasis is the hallmark of cancer that is responsible for the greatest number of cancer-related deaths. As a critical regulator of the Hippo pathway, the phosphorylation status of Yes-associated protein 1 (YAP1), mainly at S127, is critical for its oncogenic function. Herein, we aim to investigate the precise molecular mechanism between long noncoding RNA HOX transcript antisense RNA (HOTAIR) and YAP1 phosphorylation in regulating tumor migration and invasion. In this study, we showed that inhibition of HOTAIR significantly decreased the migration and invasion of cancer cells both in vitro and in vivo through elevating the phosphorylation level of YAP1 on serine 127, demonstrating a tumor suppressive role of YAP1 S127 phosphorylation. Through bisulfite sequencing PCR (BSP), we found that inhibition of HOTAIR dramatically increased Large Tumor Suppressor Kinase 1 (LATS1) expression by regulating LATS1 methylation via DNA methyltransferase 3ß (DNMT3B). In accordance with this observation, DNMT3B just only altered the distribution of YAP1 in the cytoplasm and the nucleus by inhibiting its phosphorylation, but did not change its total expression. Mechanistically, we discovered that HOTAIR suppressed YAP1 S127 phosphorylation by regulating the methylation of LATS1 via DNMT3B, the consequence of which is the translocation of YAP1 into the nucleus, reinforcing its coactivating transcriptional function, which in turn promotes the migration and invasion of cancer cells. Collectively, our data reveal that the phosphorylation of YAP1 S127 plays a vital role in the function of HOTAIR in tumorigenicity, and should be taken into consideration in future therapeutic strategies for cervical cancer.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Movimiento Celular , ADN (Citosina-5-)-Metiltransferasas , ADN Metiltransferasa 3B , Invasividad Neoplásica , Proteínas Serina-Treonina Quinasas , ARN Largo no Codificante , Factores de Transcripción , Neoplasias del Cuello Uterino , Proteínas Señalizadoras YAP , ARN Largo no Codificante/metabolismo , ARN Largo no Codificante/genética , Humanos , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/genética , Femenino , Proteínas Señalizadoras YAP/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , ADN (Citosina-5-)-Metiltransferasas/metabolismo , ADN (Citosina-5-)-Metiltransferasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Línea Celular Tumoral , Ratones , Animales , Regulación Neoplásica de la Expresión Génica , Ratones Desnudos , Fosforilación , Metilación de ADN , Ratones Endogámicos BALB C
20.
Protein Pept Lett ; 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39082173

RESUMEN

BACKGROUND: Colorectal cancer remains to be the third leading cause of cancer mortality rates. Despite the diverse effects of the miRNA cluster located in PVT1 of 8q24.21 across various tumors, the specific biological function in colorectal cancer has not been clarified. METHODS: The amplification of the miR-1204 cluster was analyzed with the cBioPortal database, while the expression and survival analysis of the miRNAs in the cluster were obtained from several GEO databases of colorectal cancer. To investigate the functional role of miR-1204 in colorectal cancer, overexpression and silencing experiments were performed by miR-1204 mimic and inhibitor transfection in colorectal cancer cell lines, respectively. Then, the effects of miR-1204 on cell proliferation were assessed through CCK-8, colony formation, and Edu assay. In addition, cell migration was evaluated using wound healing and Transwell assay. Moreover, candidate genes identified through RNA sequencing and predicted databases were identified and validated using PCR and western blot. A Dual-luciferase reporter experiment was conducted to identify MASPIN as the target gene of miR-1204. RESULT: In colorectal cancer, the miR-1204 cluster exhibited high amplification, and the expression levels of several cluster miRNAs were also significantly increased. Furthermore, miR-1204 was found to be significantly associated with disease-specific survival according to the analysis of GSE17536. Functional experiments demonstrated that transfection of miR-1204 mimic or inhibitor could enhance or decrease cancer cell proliferation and migration. MASPIN was identified as a target of miR-1204. Additionally, the overexpression of MASPIN partially rescued the effect of miR-1204 mimics on tumorigenic abilities in LOVO cells. CONCLUSION: miR-1204 positioning in 8q24.21 promotes the proliferation and migration of colorectal cancer cells by targeting MASPIN.

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