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1.
Tech Coloproctol ; 28(1): 37, 2024 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-38401006

RESUMEN

BACKGROUND: Sacral nerve neuromodulation (SNM) has been considered the optimal second-line treatment for fecal incontinence (FI). However, SNM involves high cost and requires highly skilled operators. Percutaneous tibial nerve stimulation (PTNS) has emerged as an alternative treatment modality for FI, yielding varying clinical outcomes. We conducted this meta-analysis to evaluate the effectiveness and safety of PTNS compared to sham electrical stimulation for FI. METHODS: PubMed, Embase, Web of Science, and the Cochrane Library were searched for studies from May 12, 2012 to May 12, 2022. RESULTS: Four randomized controlled studies were included in this review, involving a total of 439 adult patients with FI (300 in the PTNS group and 194 in the sham electrical stimulation group). Our meta-analysis revealed that PTNS demonstrated superior efficacy in reducing weekly episodes of FI compared to the control groups (MD - 1.6, 95% CI - 2.94 to - 0.26, p = 0.02, I2 = 30%). Furthermore, a greater proportion of patients in the PTNS group reported more than a 50% reduction in FI episodes per week (RR 0.73, 95% CI 0.57-0.94, p = 0.02, I2 = 6%). However, no significant differences were observed in any domains of the FI Quality of Life (QoL) and St Mark's incontinence scores (MD - 2.41, 95% CI - 5.1 to 0.27, p = 0.08, I2 = 67%). Importantly, no severe adverse events related to PTNS were reported in any of the participants. CONCLUSIONS: Our meta-analysis revealed that PTNS was more effective than sham stimulation in reducing FI episodes and led to a higher proportion of patients reporting more than a 50% reduction in weekly FI episodes.


Asunto(s)
Incontinencia Fecal , Estimulación Eléctrica Transcutánea del Nervio , Adulto , Humanos , Incontinencia Fecal/terapia , Incontinencia Fecal/etiología , Estimulación Eléctrica Transcutánea del Nervio/efectos adversos , Calidad de Vida , Resultado del Tratamiento , Estimulación Eléctrica , Nervio Tibial
2.
Gut ; 72(9): 1664-1677, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-36604114

RESUMEN

OBJECTIVE: Gut microbiota dysbiosis is closely linked to the pathogenesis of rheumatoid arthritis (RA). We aimed to identify potential probiotic gut microbes that can ameliorate the development of RA. DESIGN: Microbiota profiling in patients with RA and healthy individuals was investigated via 16S rDNA bacterial gene sequencing and shotgun metagenomics. Collagen-induced arthritic mice and TNF-α transgenic mice were used to evaluate the roles of the gut commensal Parabacteroides distasonis in RA. The effects of P. distasonis-derived microbial metabolites on the differentiation of CD4+ T cells and macrophage polarisation were also investigated. RESULTS: The relative abundance of P. distasonis in new-onset patients with RA and patients with RA with history of the disease was downregulated and this decrease was negatively correlated with Disease Activity Score-28 (DAS28). Oral treatment of arthritic mice with live P. distasonis (LPD) considerably ameliorated RA pathogenesis. LPD-derived lithocholic acid (LCA), deoxycholic acid (DCA), isolithocholic acid (isoLCA) and 3-oxolithocholic acid (3-oxoLCA) had similar and synergistic effects on the treatment of RA. In addition to directly inhibiting the differentiation of Th17 cells, 3-oxoLCA and isoLCA were identified as TGR5 agonists that promoted the M2 polarisation of macrophages. A specific synthetic inhibitor of bile salt hydrolase attenuated the antiarthritic effects of LPD by reducing the production of these four bile acids. The natural product ginsenoside Rg2 exhibited its anti-RA effects by promoting the growth of P. distasonis. CONCLUSIONS: P. distasonis and ginsenoside Rg2 might represent probiotic and prebiotic agents in the treatment of RA.


Asunto(s)
Artritis Reumatoide , Ratones , Animales , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Bacteroidetes , Bacterias
3.
Opt Express ; 31(22): 36810-36823, 2023 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-38017823

RESUMEN

Spatiotemporal optical vortex (STOV) pulses, possessing inherent transverse orbital angular momentum (OAM) and exhibiting phase singularity and intensity null in the spatiotemporal (ST) domain, have received increasing attention in recent years. Here, we investigate theoretically the third harmonic generation and evolution properties of STOV pulses via the interaction of 800-nm-STOV pulses with air-plasma filaments. We show that beautiful third harmonic STOV pulses are generated at a propagation distance of several millimeters. During further propagation, the ST intensity profiles of the third harmonics undergo variations in a periodic way, leading to the distortion and subsequent restoration to the initial ring pattern. The periodic evolution is a result of the interference effects between the third harmonics generated with different phases. Consequently, the evolution period is roughly twice the dephasing length of the third harmonics. Meanwhile, additional singularities emerge in the intensity patterns due to destructive interference occurring at specific dephasing lengths for the specific frequency components. The high-frequency components experience destructive interference earlier than the low-frequency components during each evolution period because the dephasing length decreases with frequency. This results in the sequentially appearance of the additional singularities from top to bottom in the ST intensity patterns. The proposed scheme demonstrates a way for higher-order STOV generation and manipulation in air-plasma filaments, which can be of interest for experiments related to vortex light science.

4.
Chem Res Toxicol ; 36(2): 141-156, 2023 02 20.
Artículo en Inglés | MEDLINE | ID: mdl-36688945

RESUMEN

The high incidence of cancer has placed an enormous health and economic burden on countries around the world. In addition to evidence of epidemiological studies, conclusive evidence from animal experiments and mechanistic studies have also shown that morbidity and mortality of some cancers can be attributed to ambient fine particulate matter (PM2.5) exposure, especially in lung cancer. However, the underlying carcinogenetic mechanisms of PM2.5 remain unclear. Furthermore, in terms of risks of other types of cancer, both epidemiological and mechanistic evidence are more limited and scattered, and the results are also inconsistent. In order to sort out the carcinogenic effect of PM2.5, this paper reviews the association of cancers with PM2.5 based on epidemiological and biological evidence including genetic, epigenetic, and molecular mechanisms. The limitations of existing researches and the prospects for the future are also well clarified in this paper to provide insights for future studies.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Neoplasias Pulmonares , Animales , Material Particulado/efectos adversos , Material Particulado/análisis , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Contaminación del Aire/efectos adversos , Exposición a Riesgos Ambientales
5.
Photochem Photobiol Sci ; 22(8): 1945-1959, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37076760

RESUMEN

Ultraviolet (UV) irradiation causes acute and chronic cutaneous effects that may result in photodamage and photoaging. Epidermis keratinocytes, as the closest surface of skin, are susceptible to damage from UV rays. Phyllanthus emblica Linn. fruit (PE) extract, as a medicine and food dual-use plant, contains high levels of polyphenols and possesses multiple pharmacological properties. The present study investigated common and different molecular mechanisms and signaling pathway activations of UVA and UVB stimulated cell damage and photoprotective effect of PE extract against UVA and UVB by Methyl Thiazolyl Tetrazolium (MTT) method, Elisa assay, flow cytometry, differentially expressed genes analysis and western blot analysis. The results showed that UVA exposure (10 J/cm2) reduced HaCaT cell viability significantly, increased the apoptosis rate, elevated intracellular reactive oxygen species level and reduced antioxidant enzyme activities. And UVA irradiation could inhibit the ERK/TGF-ß/Smad signaling pathway to downregulate collagen I, collagen III and elastin expressions, resulting in the photoaging of skin cells. We also found UVB exposure (30 mJ/cm2) caused HaCaT cell damage, promoted apoptosis, increased ROS production and induced the release of proinflammatory cytokines (IL-1α, IL-6 and PGE2). Further, in HaCaT cells, UVB ray was able to induce the activation of apoptosis markers (cleaved PARP1 and cleaved caspase3) through the MAPK/AP-1 signaling pathway using western blot analysis. Pre-treatment of PE extract prevented the UVA and UVB induced photoaging and injury in HaCaT cells through activation of ERK/TGF-ß/Smad pathway and inhibition of MAPK/AP-1 pathway, respectively. Therefore, PE extract has the potential to be used as an oral and topical preparation against skin aging and injury induced by UVA and UVB.


Asunto(s)
Phyllanthus emblica , Envejecimiento de la Piel , Phyllanthus emblica/metabolismo , Factor de Transcripción AP-1/metabolismo , Frutas/metabolismo , Queratinocitos/metabolismo , Antioxidantes/farmacología , Colágeno/farmacología , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta/farmacología , Rayos Ultravioleta/efectos adversos
6.
Macromol Rapid Commun ; 44(24): e2300449, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37792542

RESUMEN

Circularly polarized luminescence (CPL) materials with clustering-triggered emission (CTE) characteristic have gradually attracted attention for their unique photophysical properties. However, the majority of reported clusteroluminogens lack chirality and exhibit heterogeneity, making it challenging to achieve a well-defined helical structure necessary for efficient CPL with high dissymmetry factor (glum ). In this paper, chiral liquid crystals are constructed to obtain CTE-based CPL materials with high glum values. Side chain liquid crystal polymer PM6Chol bearing cholesterol clusteroluminogens are designed and synthesized. PM6Chol-coated film and PM6Chol thermal-treated film are also successfully prepared by different film-forming methods. Both the films inherit the CTE characteristic of cholesterol and show excitation wavelength-dependent luminescent behavior. However, the two polymer films exhibit different liquid crystal phase structures, with PM6Chol-coated film being a chiral bilayer smectic C phase and PM6Chol thermal-treated film being an achiral bilayer smectic A phase. Attributed to helical arrangement of cholesterol, PM6Chol-coated film emits efficient CPL with glum values up to 1.0 × 10-1 . For PM6Chol thermal-treated film, no CPL signal is detected due to the absence of helical structure. However, it shows obvious room-temperature phosphorescence with 2.0 s afterglow and 23.9 ms lifetime.


Asunto(s)
Luminiscencia , Polímeros , Temperatura , Colesterol , Análisis por Conglomerados
7.
Biochem Biophys Res Commun ; 615: 9-16, 2022 07 30.
Artículo en Inglés | MEDLINE | ID: mdl-35679751

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy driven by genetic mutations and/or epigenetic dysregulation. Gemcitabine chemotherapy is the first-line regimen for pancreatic cancer but has limited efficacy. Our previous study revealed the role of SETD2-H3K36me3 loss in the initiation and metastasis of PDAC, but little is known about its role in tumor metabolism. Here, we found that SETD2-deficient PDAC enhanced glycolysis addiction via upregulation of glucose transporter 1 (GLUT1) to meet its large demand for glucose in progression. Moreover, SETD2 deficiency impaired nucleoside synthesis by directly downregulating the transcriptional level of transketolase (TKT) in the pentose phosphate pathway. The metabolic changes confer SETD2-deficient PDAC cells with increased sensitivity to gemcitabine under glycolysis restriction conditions. Collectively, our study provides mechanistic insights into how SETD2 deficiency reprograms glycolytic metabolism to compensate for insufficient nucleoside synthesis, suggesting that glycolysis restriction combined with gemcitabine might be a potential therapeutic strategy for PDAC patients with SETD2 deficiency.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Glucólisis , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Vía de Pentosa Fosfato , Gemcitabina , Neoplasias Pancreáticas
8.
J Transl Med ; 20(1): 12, 2022 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-34980148

RESUMEN

BACKGROUND: The status of vaginal microbiota in persistent high-risk human papilloma virus (HR-HPV) infection is unclear. The present work aimed to identify the vaginal microbiota of persistent HPV infection and explore the possible underlying microbiota factors. METHODS: A total of 100 women were recruited in this study, of which 28 presented HR-HPV persistent infection (P group), 30 showed clearance of any subtype of HR-HPV (C group), and 42 had no history of any HR-HPV infection (NC group). The vaginal microbiota and the community structure of the three groups were compared based on the 16S rRNA sequencing of the V3-V4 region. The microbiota diversity and differential analysis were carried out to detect the potential factors associated with HR-HPV infection. RESULTS: P and C groups showed an increase of Firmicutes and Actinobacteriota but a decrease in Proteobacteria compared to the NC group. The Chao1 index indicated that the microbial richness of the NC group was greater than C group (P < 0.05).The principal co-ordinate analysis(PCoA) revealed differences between the NC and P/C groups.The linear discriminant analysis effect size (LEfSe) method indicated that Proteobacteria phylum was significantly different in the mean relative abundance in the NC group,but the P and C groups did not show such indicative taxa. The Wilcox rank-sum test indicated that the Bifidobacterium (P = 0.002) and Lactobacillus (P = 0.005) of the C group were in a high mean relative abundance compared to the NC group. CONCLUSIONS: The persistent HR-HPV infection is associated with dysbiosis of the vaginal microbiota. Microbiome regulation with Bifidobacteria and Lactobacillus may affect the clearance of HPV.


Asunto(s)
Microbiota , Infecciones por Papillomavirus , Disbiosis , Femenino , Humanos , Papillomaviridae , ARN Ribosómico 16S/genética , Vagina/microbiología
9.
Opt Express ; 30(6): 9727-9744, 2022 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-35299392

RESUMEN

We propose a scheme to manipulate the local orbital angular momentum (OAM) of the ultra-broadband (0.1-30 THz) terahertz (THz) waves from the laser-induced short air filament via chirping the few-cycle vortex laser pump. The simulation results show that either the THz vortex pulses with linear azimuth-dependent phases or the THz angular accelerating vortex beams (AAVBs) with nonlinear azimuth-dependent phases can be produced by tuning the chirp parameter of the pump. Thus, the dominant physical mechanism for THz generation can be determined. The THz temporal and transverse spatial distributions can be also controlled by the chirp parameter. Furthermore, their local OAM density distributions present very complex structures because most of the modulated azimuthal intensity and the corresponding local angular helicity distributions are not able to cancel out completely. Via analyzing the simulated THz results at the different pump intensities, we classify the initial pump intensity into three cases. For the low intensity case, the Kerr effect comes into prominence, so the generated THz radiation shall be vortex pulses. While for the high intensity case, the leading plasma effect dominates. In contrast, when the pump intensity is at the medium level, the Kerr nonlinearity and the plasma effect may be comparable and competitive. Basically, THz AAVBs are generated for both high and medium intensity cases. Our study will provide the possibility for studying the optically induced rotation technology more intuitively from the perspective of angular momentum transfer.

10.
Phys Rev Lett ; 128(17): 174801, 2022 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-35570418

RESUMEN

Electron beam longitudinal polarization during the interaction with counterpropagating circularly polarized ultraintense laser pulses is investigated, while accounting for the anomalous magnetic moment of the electron. Although it is known that the helicity transfer from the laser photons to the electron beam is suppressed in linear and nonlinear Compton scattering processes, we show that the helicity transfer nevertheless can happen via an intermediate step of the electron radiative transverse polarization, phase matched with the driving field, followed up by spin rotation into the longitudinal direction as induced by the anomalous magnetic moment of the electron. With spin-resolved QED Monte Carlo simulations, we demonstrate the consequent helicity transfer from laser photons to the electron beam with a degree up to 10%, along with an electron radial polarization up to 65% after multiple photon emissions in a femtosecond timescale. This effect is detectable with currently achievable laser facilities, evidencing the role of the leading QED vertex correction to the electron anomalous magnetic moment in the polarization dynamics in ultrastrong laser fields.

11.
Langmuir ; 38(46): 14326-14334, 2022 11 22.
Artículo en Inglés | MEDLINE | ID: mdl-36355865

RESUMEN

Combination chemotherapy is recognized as a vital medical treatment for cancer, but it has not achieved clinical ideal effects of combination therapy. Herein, we designed a supramolecular combination chemotherapy strategy based on cucurbit[8]uril (CB[8]), which can be facilely assembled into dual platinum drugs. Interestingly, employing the CB[8] carrier led to a greater than 10-fold intracellular Pt content compared to that of dual drugs at 4 h, and the CB[8] complex (CLE) can enhance the infiltration of platinum drugs in colorectal tumor cells tremendously. The platinum drugs can be released from CLE through consuming more tumor biomarker spermidine. Through analyzing the nanomechanical property of the colorectal tumor cellular surface by bioscope AFM, it was revealed that CLE modified the property by decreasing the adhesion and increasing the stiffness. This study provided a facile and sensitive strategy for improving combination chemotherapy by supramolecular materials.


Asunto(s)
Neoplasias Colorrectales , Platino (Metal) , Humanos , Hidrocarburos Aromáticos con Puentes , Imidazoles , Neoplasias Colorrectales/tratamiento farmacológico
12.
Int J Clin Pharmacol Ther ; 60(3): 146-158, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34846299

RESUMEN

OBJECTIVE: Previous clinical studies and meta-analyses have shown controversial results on the association between C3435T polymorphism of the ABCB1 gene and anti-epileptic drug (AED) resistance. Based on the fact that sample size and confounding factors could contribute to the inconsistency, we performed an updated meta-analysis by including the most recent studies, and subgroup analysis was conducted to evaluate the effect of confounding factors on the association. MATERIALS AND METHODS: We searched articles in 6 electronic databases including PubMed, Medline, Embase, Web of science, Cochrane Library, CNKI (China National Knowledge Infrastructure) for relevant articles up to June 2020. RESULTS: The current analysis showed that the C allele of C3435T variant was a risk factor for drug resistance in the overall populations (C allele vs. T allele, OR: 1.13; 95% CI: 1.02 - 1.25; p = 0.02) and in the Caucasians (C allele vs. T allele, OR: 1.09; 95% CI: 1.09 - 1.43; p = 0.002), while no association was observed in Asians and Indians. Particularly, our study reported for the first time that the 3435T allele was more common in epilepsy patients with drug resistance in the Tunisian population (C allele vs. T allele, OR: 0.31; 95% CI: 0.15 - 0.65; p = 0.002). In addition, our present analysis suggested an association between C3435T and AED resistance in cryptogenic, symptomatic, but not in idiopathic patients. Subgroup studies based on age and gender showed no association. CONCLUSION: AED resistance in Caucasian and Tunisian populations may benefit from ABCB1 C3435T genotyping. We recommend that more details, such as gender and etiology of epilepsy, should be taken into account to draw a reliable conclusion in future studies.


Asunto(s)
Anticonvulsivantes , Epilepsia , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Anticonvulsivantes/efectos adversos , Pueblo Asiatico/genética , Resistencia a Medicamentos/genética , Epilepsia/tratamiento farmacológico , Epilepsia/genética , Predisposición Genética a la Enfermedad , Humanos , Polimorfismo de Nucleótido Simple
13.
Plant J ; 103(1): 95-110, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-31999384

RESUMEN

Taxus stem barks can be used for extraction of paclitaxel. However, the composition of taxoids across the whole stem and the stem tissue-specificity of paclitaxel biosynthesis-related enzymes remain largely unknown. We used cultivated Taxus media trees for analyses of the chemical composition and protein of major stem tissues by an integrated metabolomic and proteomic approach, and the role of TmMYB3 in paclitaxel biosynthesis was investigated. The metabolomic landscape analysis showed differences in stem tissue-specific accumulation of metabolites. Phytochemical analysis revealed that there is high accumulation of paclitaxel in the phloem. Ten key enzymes involved in paclitaxel biosynthesis were identified, most of which are predominantly produced in the phloem. The full-length sequence of TmMYB3 and partial promoter sequences of five paclitaxel biosynthesis-related genes were isolated. Several MYB recognition elements were found in the promoters of TBT, DBTNBT and TS. Further in vitro and in vivo investigations indicated that TmMYB3 is involved in paclitaxel biosynthesis by activating the expression of TBT and TS. Differences in the taxoid composition of different stem tissues suggest that the whole stem of T. media has potential for biotechnological applications. Phloem-specific TmMYB3 plays a role in the transcriptional regulation of paclitaxel biosynthesis, and may explain the phloem-specific accumulation of paclitaxel.


Asunto(s)
Paclitaxel/biosíntesis , Floema/metabolismo , Proteínas de Plantas/metabolismo , Tallos de la Planta/metabolismo , Taxus/metabolismo , Factores de Transcripción/metabolismo , Regulación de la Expresión Génica de las Plantas/genética , Redes y Vías Metabólicas , Metabolómica , Proteínas de Plantas/fisiología , Regiones Promotoras Genéticas , Proteómica , Factores de Transcripción/fisiología
14.
BMC Plant Biol ; 21(1): 104, 2021 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-33622251

RESUMEN

BACKGROUND: Taxol is an efficient anticancer drug accumulated in Taxus species. Pseudotaxus chienii is an important member of Taxaceae, however, the level of six taxoids in P. chienii is largely unknown. RESULTS: High accumulation of 10-DAB, taxol, and 7-E-PTX suggested that P. chienii is a good taxol-yielding species for large-scale cultivation. By the omics approaches, a total of 3,387 metabolites and 61,146 unigenes were detected and annotated. Compared with a representative Taxus tree (Taxus yunnanensis), most of the differentially accumulated metabolites and differential expressed genes were assigned into 10 primary and secondary metabolism pathways. Comparative analyses revealed the variations in the precursors and intermediate products of taxol biosynthesis between P. chienii and T. yunnanensis. Taxusin-like metabolites highly accumulated in P. chienii, suggesting a wider value of P. chienii in pharmaceutical industry. CONCLUSIONS: In our study, the occurrence of taxoids in P. chienii was determined. The differential expression of key genes involved in the taxol biosynthesis pathway is the major cause of the differential accumulation of taxoids. Moreover, identification of a number of differentially expressed transcription factors provided more candidate regulators of taxol biosynthesis. Our study may help to reveal the differences between Pseudotaxus and Taxus trees, and promote resource utilization of the endangered and rarely studied P. chienii.


Asunto(s)
Vías Biosintéticas , Metaboloma , Metabolómica , Paclitaxel/biosíntesis , Plantas Medicinales/metabolismo , Especificidad de la Especie , Taxaceae/metabolismo , Especies en Peligro de Extinción , Variación Genética
15.
Langmuir ; 37(31): 9547-9552, 2021 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-34333979

RESUMEN

Supramolecular chemotherapy has drawn increasing interest due to its ability to improve the efficiency of antitumor drugs and fewer associated toxic side effects. In this study, the smart supramolecular cargo, the doxorubicin-ZnO-cucurbit[7]uril (CDZ) nanocomplex, was constructed through ion-dipole interactions between cucurbit[7]uril {CB[7]} and doxorubicin-ZnO (dox-ZnO). The binding affinity of CB[7] and dox-ZnO was determined to be 104 M-1 by isothermal titration calorimetry. Importantly, spermine had a stronger binding affinity (106 M-1) with CB[7] than dox-ZnO through host-guest interactions. In the tumor microenvironment, spermine disassembled the CDZ nanocomplex, and dox was released from the nanocomplex by XRD, UV-visible spectra, and contact angle analysis. Compared to the single drug dox, the CDZ nanocomplex was demonstrated to possess higher activity of killing colorectal tumor cells by confocal laser scanning microscopy and cytotoxicity, which could be attributed to spermine concentration, spermine synthase, free radical damage, and G1 cell cycle arrest. Overall, the supramolecular delivery of dox can enhance the inhibition of human colorectal tumor cell proliferation and reduce cytotoxicity in human myocardial cells through the noncovalent bond synergy of {CB[7]}.


Asunto(s)
Hidrocarburos Aromáticos con Puentes , Neoplasias Colorrectales , Neoplasias Colorrectales/tratamiento farmacológico , Doxorrubicina/farmacología , Humanos , Imidazoles , Microambiente Tumoral
16.
Langmuir ; 37(18): 5475-5482, 2021 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-33913723

RESUMEN

Supramolecular chemotherapy is a strategy that is currently used to improve the therapeutic efficacy of traditional chemotherapy while mitigating side effects. Heptaplatin, a platinum chemotherapeutic antitumor drug in colorectal tumors, is traditionally used in the clinic. However, its side effects and low efficiency in killing tumors remain unresolved. Herein, a facile supramolecular chemotherapy platform on account of the host-guest chemistry between cucurbit[7]uril and the commercially available heptaplatin was studied. At pH 7.4, heptaplatin showed a strong binding to the cucurbit[7]uril nanocarrier by 1H NMR, whose Ka was (1.38 ± 0.06) × 106 M-1 by isothermal titration calorimetry (ITC). At pH 6.0 in a tumor microenvironment, overexpressed spermine can exchange competitively heptaplatin from heptaplatin-CB[7]. This supramolecular complex achieved higher antitumor activity on colorectal tumor cells and lower cytotoxicity than the drug alone on colorectal normal cells. Furthermore, the antitumor mechanisms of supramolecular complex were investigated by apoptosis, cell cycle, and spermine synthase. It was found that heptaplatin-CB[7] consumed more colorectal tumorous intracellular spermine by the spermine synthase assay (413.85 ± 0.004 pg/mL); hepataplatin-CB[7] caused early apoptosis (87.73%) of colorectal tumor cells; heptaplatin-CB[7] induced an inhibitory response in the G1 phase of the tumor cell cycle. These findings demonstrated that heptaplatin-CB[7] had higher antitumor activity toward human colorectal tumor cells but lower cytotoxicity toward human colorectal normal cells. It is expected to promote the supramolecular chemotherapy and translational development of the nanocomplex into the clinical field.


Asunto(s)
Hidrocarburos Aromáticos con Puentes , Neoplasias Colorrectales , Neoplasias Colorrectales/tratamiento farmacológico , Humanos , Imidazoles , Malonatos , Compuestos Organoplatinos , Microambiente Tumoral
17.
Biomed Chromatogr ; 35(11): e5193, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34128252

RESUMEN

In this study, a simple and sensitive analytical method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated for the determination of neferine in rat plasma. After acetonitrile-mediated protein precipitation, the samples were separated on an Acquity BEH C18 column (2.1 × 50 mm, 1.7 µm) maintained at 40°C. The mobile phase comprising 0.1% formic acid in water and acetonitrile was delivered at a flow rate of 0.4 ml/min. The mass detection was conducted using multiple reaction monitoring mode with ion transitions at 625.4 > 206.3 and m/z 622.9 > 380.9 for neferine and internal standard, respectively. The assay was demonstrated to be linear over the concentration range of 0.5-1,000 ng/ml, with correlation coefficient >0.999 (r > 0.999). The validated method was further applied to the pharmacokinetic study of neferine in rat plasma. In addition, the metabolism of neferine was investigated using high-resolution mass spectrometry. A total of six metabolites from rat liver microsomes and plasma were detected and their structures were identified according to their fragment ions. The proposed metabolic pathways of neferine were demethylation, dealkylation, dehydrogenation and glucuronidation.


Asunto(s)
Bencilisoquinolinas , Cromatografía Liquida/métodos , Espectrometría de Masas en Tándem/métodos , Animales , Bencilisoquinolinas/análisis , Bencilisoquinolinas/química , Bencilisoquinolinas/farmacocinética , Disponibilidad Biológica , Límite de Detección , Modelos Lineales , Masculino , Microsomas Hepáticos/metabolismo , Ratas , Ratas Sprague-Dawley , Reproducibilidad de los Resultados
18.
Phys Rev Lett ; 125(4): 044802, 2020 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-32794799

RESUMEN

The production of a highly polarized positron beam via nonlinear Breit-Wheeler processes during the interaction of an ultraintense circularly polarized laser pulse with a longitudinally spin-polarized ultrarelativistic electron beam is investigated theoretically. A new Monte Carlo method employing fully spin-resolved quantum probabilities is developed under the local constant field approximation to include three-dimensional polarization effects in strong laser fields. The produced positrons are longitudinally polarized through polarization transferred from the polarized electrons by the medium of high-energy photons. The polarization transfer efficiency can approach 100% for the energetic positrons moving at smaller deflection angles. This method simplifies the postselection procedure to generate high-quality positron beams in further applications. In a feasible scenario, a highly polarized (40%-65%), intense (10^{5}-10^{6}/bunch), collimated (5-70 mrad) positron beam can be obtained in a femtosecond timescale. The longitudinally polarized positron sources are desirable for applications in high-energy physics and material science.

19.
Phys Rev Lett ; 124(1): 014801, 2020 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-31976698

RESUMEN

Generation of circularly polarized (CP) and linearly polarized (LP) γ rays via the single-shot interaction of an ultraintense laser pulse with a spin-polarized counterpropagating ultrarelativistic electron beam has been investigated in nonlinear Compton scattering in the quantum radiation-dominated regime. For the process simulation, a Monte Carlo method is developed which employs the electron-spin-resolved probabilities for polarized photon emissions. We show efficient ways for the transfer of the electron polarization to the high-energy photon polarization. In particular, multi-GeV CP (LP) γ rays with polarization of up to about 95% can be generated by a longitudinally (transversely) spin-polarized electron beam, with a photon flux meeting the requirements of recent proposals for the vacuum birefringence measurement in ultrastrong laser fields. Such high-energy, high-brilliance, high-polarization γ rays are also beneficial for other applications in high-energy physics, and laboratory astrophysics.

20.
Environ Sci Technol ; 54(14): 8558-8567, 2020 07 21.
Artículo en Inglés | MEDLINE | ID: mdl-32589839

RESUMEN

Modifications of the physicochemical properties and oxidative potential (OP) of soot due to visible-light irradiation and its underlying mechanisms during atmospheric aging have not been elucidated. In this study, two types of soot obtained using different air/fuel ratios (A/F) were aged under visible light with or without ozone (O3) at an atmospherically relevant level in an environmental chamber. Physicochemical characteristics and OP of aged soot were systematically measured using the dithiothreitol (DTT) assay (OPDTT). Regardless of the presence of O3, visible light markedly promoted oxidation of soot, which led to consumption of polycyclic aromatic hydrocarbons, formation of oxygen-containing functional groups, and enhancement of OPDTT values. Compared to low-A/F soot, high-A/F soot contained more elemental carbon but less organic carbon and was more sensitive to visible light by exhibiting greater changes. It was proposed that elemental carbon in soot under visible-light irradiation initiated an inside-to-outside oxidation pathway, where reactive oxygen species played an important role. This study clarified the solar irradiation-triggered self-oxidation process in soot, which is important to its atmospheric and health effects.


Asunto(s)
Ozono , Hollín , Oxidación-Reducción , Estrés Oxidativo , Especies Reactivas de Oxígeno
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