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1.
Endocrine ; 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38649647

RESUMEN

BACKGROUND: Thyroid dysfunction's effects on those who have been diagnosed with atrial fibrillation have not been well investigated. We looked at how thyroid function among patients with pre-existing atrial fibrillation related to thromboembolic risk and clinical outcomes. METHODS: We gathered the medical information of patients diagnosed with nonvalvular atrial fibrillation (NVAF) between 2016 and 2020 at Dongguan People's Hospital. We then assessed the correlation between thyroid dysfunction and thrombotic risk (CHA2DS2-VASc) as well as the occurrence of clinical composite endpoint (all-cause death, heart failure, systemic embolism and hemorrhage events). RESULTS: Of 1329 patients were admitted, 82.6% were euthyroid, 7.4% had subclinical hyperthyroidism, 4.2% had subclinical hypothyroidism, and 6.7% had low triiodothyronine (T3) syndrome. Lower levels of total triiodothyronine (TT3) were linked to an increased risk of thromboembolism (P < 0.005). During a median follow-up period of 1.84 years, there were 608 clinical composite endpoint occurrences. In the adjusted model, Low T3 syndrome was linked to a higher risk of the clinical composite endpoint (HR, 1.68; 95% CI, 1.20-2.37; P < 0.05) in comparison to euthyroidism. Specifically, low T3 syndrome was linked to a higher risk of heart failure (HR, 1.52; 95%CI, 1.01-2.30; P < 0.05) and all-cause death (HR, 3.34; 95% CI, 1.76-6.36; P < 0.001). CONCLUSION: Low T3 syndrome are linked to an increased risk of heart failure and all-cause death in individuals with NVAF. And Patients with NVAF and low TT3 levels have a higher risk of thromboembolism.

2.
Nat Sci Sleep ; 16: 279-289, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38495839

RESUMEN

Objective: To examine the relationship between pregnancy-related anxiety, family functions, and sleep quality, and to determine whether family functions mediate the relationship between pregnancy-related anxiety and sleep quality. Methods: A cross-sectional survey was conducted on pregnant women between April to August in 2022 in the obstetrics outpatient clinic of a tertiary care hospital in the Ningxia Hui Autonomous Region of China. A total of 1014 pregnant women aged 18 years and older were surveyed. They completed questionnaires, including: general demographic characteristics, the Pregnancy-related anxiety scale (PAQ), the Family Adaptation, Partnership, Growth, Affection, and Resolve (APGAR), and the Pittsburgh Sleep Quality Index Questionnaire (PSQI). Model 4 in PROCESS was used to analyze the relationships among pregnancy-related anxiety, family functions, and sleep quality, with family functions as a mediator. Results: Among the 1014 pregnant women, the pregnancy-related anxiety scale score was (21.84 ± 5.64). The total score of the family functions scale was (8.10±2.26), and the overall sleep quality scale score was (7.89±2.99). When participants were grouped according to different socio-demographic characteristics, the study showed that all variables differed from anxiety, family functions or sleep quality, except for age, pre-pregnancy BMI and whether or not they had a first birth, which was not associated with anxiety, family functions, or sleep quality (P<0.05). The pregnancy-related anxiety was positively associated with sleep quality (P<0.01), while family functions were negatively associated with sleep quality (P<0.01). In addition, family functions mediate the relationship between pregnancy-related anxiety and sleep quality during pregnancy, on the first and second trimesters, intermediation rate is 9.31% (P<0.05), and on the third trimesters, intermediation rate is 21.38% (P<0.05). Conclusion: Pregnancy- related anxiety is a risk factor for sleep quality, however, family functions are protective factors for sleep quality. Family functions play an intermediary role in sleep quality caused by pregnancy-related anxiety, especially on the third trimesters. This finding may provide a scientific basis for developing intervention strategies to improve the sleep quality of pregnant women.

3.
Int Immunopharmacol ; 126: 111308, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38061121

RESUMEN

Maternal immune activation (MIA), defined as elevated levels of inflammatory markers beyond the normal range, can occur due to psychological stress, infection, and other disruptions during pregnancy. MIA affects the immune system development in offspring and increases the risk of immune-related disorders. Limited studies have investigated the effects of prenatal stress on offspring's immune system. In this study, pregnant rats were exposed to chronic unpredictable mild stress (CUMS) during pregnancy, involving seven different stressors. We examined the impact of prenatal stress stimuli on the offspring's immune system and observed activation of the PI3K/Akt/NF-κB signaling pathway, resulting in an imbalance of Th17/Treg cells in the offspring's spleen. Our findings revealed increased plasma levels of corticosterone, IL-1ß, and IL-6 in female rats exposed to prenatal stress, as well as elevated serum levels of IL-6 and TNF-α in the offspring. Furthermore, we identified a correlation between cytokine levels in female rats and their offspring. Transcriptome sequencing and qPCR experiments indicated differentially expressed mRNAs in offspring exposed to prenatal stress, which may contribute to the imbalance of Th17/Treg cells through the activation of the Gng3-related PI3K/Akt/NF-κB pathway.


Asunto(s)
FN-kappa B , Proteínas Proto-Oncogénicas c-akt , Embarazo , Ratas , Femenino , Animales , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Interleucina-6 , Linfocitos T Reguladores/metabolismo , Transducción de Señal
4.
PeerJ ; 11: e14757, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36718441

RESUMEN

In order to understand the adaptative changes of the Japanese yew (Taxus cuspidate L.) to high light conditions, this study investigated gas-exchange, chlorophyll fluorescence, chlorophyll, and the impact of epicuticular wax on the gas-exchange and photoinhibition of Japanese yew seedlings and saplings. The chlorophyll content per unit area and photosynthetic rate in seedling leaves were significantly lower than in sapling leaves. When leaves from seedlings and saplings were exposed to 1,200 µmol·m-2·s-1 photon flux density (PFD) for 2 h, seedling leaves exhibited a greater down-regulation of maximum quantum yield (Fv/Fm) and actual photosystem II efficiency ( Φ PSII). Non-photochemical quenching (NPQ) and high energy quenching (qE) in sapling leaves were much higher than in seedling leaves when both were exposed to 1,200 µmol·m-2·s-1 PFD for 2 h. At a low level of O2, the photorespiration rate (Pr) and the ratio of photorespiration/gross photosynthetic rate (Pr/Pg) in seedling leaves were lower than in sapling leaves when both were exposed to 1,200 µmol·m-2·s-1 PFD, but this difference did not reach statistical significance (P < 0.05). Compared with sapling leaves, seedling leaves exhibited lower levels of xanthophyll pool. Epicuticular wax content on seedling leaves was significantly lower than on sapling leaves. The results of this study showed that wax coverage on the leaf surface decreased the photosynthetic rate in sapling leaves as a consequence of decreased stomatal conductance. Epicuticular wax is related to tree age and photoinhibition prevention in the Japanese yew. It is possible that lower photosynthetic rate, lower NPQ depending on the xanthophyll cycle, and lower deposition of epicuticular wax results in seedling plants that are not adapted to high light conditions.


Asunto(s)
Plantones , Taxus , Humanos , Clorofila/fisiología , Fotosíntesis/fisiología , Plantones/metabolismo , Taxus/metabolismo , Xantófilas/metabolismo
5.
Colloids Surf B Biointerfaces ; 217: 112667, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35816881

RESUMEN

In recent years, manganese dioxide (MnO2) nanoparticles with unique physicochemical properties have been widely used in many biomedical fields, such as biosensors, contrast agents, tumor therapy, and drug delivery. From these applications, MnO2 nanoparticles have great clinical translation potential. However, by contrast, the in vitro and in vivo biosafety of MnO2 nanoparticles have been deeply and thoroughly clarified for the clinical translation, which hinders their clinical applications. In this work, we deeply investigated the blood safety of MnO2 nanoparticles by conducting a series of in vitro and in vivo experiments. These included the effects of MnO2 nanoparticles on morphology of red blood cells, activation of platelets, coagulation functions, and toxicity of key organs. The obtained results show that these effects displayed a concentration-dependent manner of MnO2 nanoparticles. Different safe concentration ranges could be found in the different experimental index. This study provides important guidance for the specific biomedical applications of MnO2 nanoparticles, greatly accelerating their laboratory development and clinical translation.


Asunto(s)
Compuestos de Manganeso , Nanopartículas , Sistemas de Liberación de Medicamentos , Compuestos de Manganeso/química , Compuestos de Manganeso/farmacología , Nanopartículas/química , Óxidos/química , Porosidad
6.
Cells ; 11(8)2022 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-35456000

RESUMEN

Maize yield is significantly influenced by low temperature, particularly chilling stress at the maize seedling stage. Various physiological approaches have been established to resist chilling stress; however, the detailed proteins change patterns underlying the maize chilling stress response at the seedling stage remain unknown, preventing the development of breeding-based methods to resist chilling stress in maize. Thus, we performed comprehensive physiological, comparative proteomics and specific phytohormone abscisic acid (ABA) assay on different maize inbred lines (tolerant-line KR701 and sensitive-line hei8834) at different seedling stages (the first leaf stage and third leaf stage) under chilling stress. The results revealed several signalling proteins and pathways in response to chilling stress at the maize seedling stage. Meanwhile, we found ABA pathway was important for chilling resistance of tolerant-line KR701 at the first leaf stage. Related chilling-responsive proteins were further catalogued and analysed, providing a resource for further investigation and maize breeding.


Asunto(s)
Proteómica , Zea mays , Ácido Abscísico/metabolismo , Genotipo , Proteómica/métodos , Plantones/genética , Zea mays/genética
7.
Bioengineered ; 12(2): 12407-12419, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34905428

RESUMEN

This study aims to explore the effect of N-terminal pro-brain natriuretic peptide (NT-proBNP) variability (mean absolute difference of the log2 NT-proBNP level measured in hospital) on the prognosis of patients with cardiorenal syndrome (CRS) type 2. Patients with CRS type 2 were retrospectively included. The varied NT-proBNP indications were analyzed. They were NT-proBNP I(pre-treatment), NT-proBNP II(post-treatment), NT-proBNP II/I, ΔNT-proBNP, log2 (NT-proBNP) variability and mean log2 (NT-proBNP). A logistic regression model and survival curves (Kaplan-Meier analysis) were built to identify independent predictors associated with poor prognosis. The primary outcomes were major adverse renal and cardiac events. The secondary outcome was all-cause mortality. From 2012 to 2016, 136 patients were included in this study with 69 (50.7%) had high log2 (NT-proBNP) variability level. The optimal cutoff level for each NT-proBNP indication that predicts poor prognosis was calculated, and the area under curves ranged from 0.668 to 0.891 with different indications. Kaplan-Meier analysis revealed that there was significantly correlated with prevalence of primary outcomes and NT-proBNP variability. The hazard ratios (HRs) ranged from 1.67 to 6.61 with different indications. The multivariate regression analyses also identified the risk of the primary outcomes were associated with elevated NT-proBNP values, except NT-proBNP I. The odds ratio (ORs) ranged from 1.83 to 6.61 with different indications. When analyzing the relationship between NT-proBNP variability and all-cause mortality, the results were the same. NT-proBNP variability might serve as an independent predictor for poor prognosis and all-cause mortality in patients with CRS type 2.


Asunto(s)
Síndrome Cardiorrenal/metabolismo , Péptido Natriurético Encefálico/metabolismo , Fragmentos de Péptidos/metabolismo , Anciano , Biomarcadores/metabolismo , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Análisis Multivariante , Oportunidad Relativa , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROC , Estudios Retrospectivos , Medición de Riesgo
8.
Int J Mol Sci ; 22(19)2021 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-34638657

RESUMEN

Phytohormone ABA regulates the expression of numerous genes to significantly affect seed dormancy, seed germination and early seedling responses to biotic and abiotic stresses. However, the function of many ABA-responsive genes remains largely unknown. In order to improve the ABA-related signaling network, we conducted a large-scale ABA phenotype screening. LSH, an important transcription factor family, extensively participates in seedling development and floral organogenesis in plants, but whether its family genes are involved in the ABA signaling pathway has not been reported. Here we describe a new function of the transcription factor LSH8 in an ABA signaling pathway. In this study, we found that LSH8 was localized in the nucleus, and the expression level of LSH8 was significantly induced by exogenous ABA at the transcription level and protein level. Meanwhile, seed germination and root length measurements revealed that lsh8 mutant lines were ABA insensitive, whereas LSH8 overexpression lines showed an ABA-hypersensitive phenotype. With further TMT labeling quantitative proteomic analysis, we found that under ABA treatment, ABA-responsive proteins (ARPs) in the lsh8 mutant presented different changing patterns with those in wild-type Col4. Additionally, the number of ARPs contained in the lsh8 mutant was 397, six times the number in wild-type Col4. In addition, qPCR analysis found that under ABA treatment, LSH8 positively mediated the expression of downstream ABA-related genes of ABI3, ABI5, RD29B and RAB18. These results indicate that in Arabidopsis, LSH8 is a novel ABA regulator that could specifically change the expression pattern of APRs to positively mediate ABA responses.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Transducción de Señal/fisiología , Factores de Transcripción/metabolismo , Regulación de la Expresión Génica de las Plantas/fisiología , Germinación/fisiología , Fenotipo , Proteómica/métodos , Semillas/metabolismo
9.
Mol Cell Biochem ; 476(12): 4245-4263, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34351574

RESUMEN

Kawasaki disease (KD) causes cardiovascular system injury in children. However, the pathogenic mechanisms of KD have not been well defined. Recently, strong correlation between aberrant microRNAs and KD nosogenesis has been revealed. A role of microRNA-197-3p (miR-197-3p) in the pathogenesis of KD is identified in the present study. Cell proliferation assay showed human coronary artery endothelial cells (HCAECs) were suppressed by serum from KD patients, which was correlated with high levels of miR-197-3p in both KD serum and HCAECs cultured with KD serum. The inhibition of HCAECs by miR-197-3p was confirmed by cells expressing miR-197-3p mimic and miR-197-3p inhibitor. Comparative proteomics analysis and Ingenuity Pathway Analysis (IPA) revealed TIMP3 as a potential target of miR-197-3p, which was demonstrated by western blot and dual-luciferase reporter assays. Subsequently, by detecting the endothelium damage markers THBS1, VWF, and HSPG2, the role of miR-197-3p/TIMP3 in KD-induced damage to HCAECs was confirmed, which was further validated by a KD mouse model in vivo. The expressions of miR-197-3p and its target, TIMP3, are dramatically variational in KD serum and HCAECs cultured with KD serum. Increased miR-197-3p induces HCAECs abnormal by restraining TIMP3 expression directly. Hence, dysregulation of miR-197-3p/TIMP3 expression in HCAECs may be an important mechanism in cardiovascular endothelium injury in KD patients, which offers a feasible therapeutic target for KD treatment.


Asunto(s)
Enfermedad de la Arteria Coronaria/patología , Células Endoteliales/patología , MicroARNs/genética , Síndrome Mucocutáneo Linfonodular/patología , Proteoma/metabolismo , Inhibidor Tisular de Metaloproteinasa-3/antagonistas & inhibidores , Animales , Apoptosis/fisiología , Células Cultivadas , Preescolar , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/inmunología , Enfermedad de la Arteria Coronaria/metabolismo , Células Endoteliales/inmunología , Células Endoteliales/metabolismo , Femenino , Humanos , Lactante , Masculino , Ratones , Ratones Endogámicos C57BL , MicroARNs/sangre , Síndrome Mucocutáneo Linfonodular/etiología , Síndrome Mucocutáneo Linfonodular/metabolismo , Proteoma/análisis , Inhibidor Tisular de Metaloproteinasa-3/genética , Inhibidor Tisular de Metaloproteinasa-3/metabolismo
10.
Int J Mol Sci ; 22(16)2021 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-34445714

RESUMEN

Phytochromobilin (PΦB) participates in the regulation of plant growth and development as an important synthetase of photoreceptor phytochromes (phy). In addition, Arabidopsis long hypocotyl 2 (HY2) appropriately works as a key PΦB synthetase. However, whether HY2 takes part in the plant stress response signal network remains unknown. Here, we described the function of HY2 in NaCl signaling. The hy2 mutant was NaCl-insensitive, whereas HY2-overexpressing lines showed NaCl-hypersensitive phenotypes during seed germination. The exogenous NaCl induced the transcription and the protein level of HY2, which positively mediated the expression of downstream stress-related genes of RD29A, RD29B, and DREB2A. Further quantitative proteomics showed the patterns of 7391 proteins under salt stress. HY2 was then found to specifically mediate 215 differentially regulated proteins (DRPs), which, according to GO enrichment analysis, were mainly involved in ion homeostasis, flavonoid biosynthetic and metabolic pathways, hormone response (SA, JA, ABA, ethylene), the reactive oxygen species (ROS) metabolic pathway, photosynthesis, and detoxification pathways to respond to salt stress. More importantly, ANNAT1-ANNAT2-ANNAT3-ANNAT4 and GSTU19-GSTF10-RPL5A-RPL5B-AT2G32060, two protein interaction networks specifically regulated by HY2, jointly participated in the salt stress response. These results direct the pathway of HY2 participating in salt stress, and provide new insights for the plant to resist salt stress.


Asunto(s)
Arabidopsis/genética , Arabidopsis/metabolismo , Oxidorreductasas/genética , Oxidorreductasas/metabolismo , Sequías , Germinación/fisiología , Oxidorreductasas/fisiología , Fitocromo/metabolismo , Desarrollo de la Planta/efectos de los fármacos , Plantas Modificadas Genéticamente , Estrés Salino/efectos de los fármacos , Estrés Salino/genética , Estrés Salino/fisiología , Semillas/metabolismo , Transducción de Señal/fisiología , Cloruro de Sodio/metabolismo , Estrés Fisiológico/genética
11.
Sci Rep ; 11(1): 1764, 2021 01 19.
Artículo en Inglés | MEDLINE | ID: mdl-33469070

RESUMEN

Maize is China's largest grain crop. Mechanical grain harvesting is the key technology in maize production, and the kernel moisture concentration (KMC) is the main controlling factor in mechanical maize harvesting in China. The kernel dehydration rate (KDR) is closely related to the KMC. Thus, it is important to conduct genome-wide association studies (GWAS) of the KMC and KDR in maize, detect relevant quantitative trait nucleotides (QTNs), and mine relevant candidate genes. Here, 132 maize inbred lines were used to measure the KMC every 5 days from 10 to 40 days after pollination (DAP) in order to calculate the KDR. These lines were genotyped using a maize 55K single-nucleotide polymorphism array. QTNs for the KMC and KDR were detected based on five methods (mrMLM, FASTmrMLM, FASTmrEMMA, pLARmEB, and ISIS EM-BLASSO) in the package mrMLM. A total of 334 significant QTNs were found for both the KMC and KDR, including 175 QTNs unique to the KMC and 178 QTNs unique to the KDR; 116 and 58 QTNs were detected among the 334 QTNs by two and more than two methods, respectively; and 9 and 5 QTNs among 58 QTNs were detected in 2 and 3 years, respectively. A significant enrichment in cellular component was revealed by Gene Ontology enrichment analysis of candidate genes in the intervals adjacent to the 14 QTNs and this category contained five genes. The information provided in this study may be useful for further mining of genes associated with the KMC and KDR in maize.

12.
Br J Pharmacol ; 178(2): 328-345, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33068011

RESUMEN

BACKGROUND AND PURPOSE: Acute kidney injury (AKI) is a common and critical illness, resulting in severe morbidity and a high mortality. There is a considerable interest in identifying novel molecular targets for management of AKI. We investigated the potential role of the circadian clock components Rev-erb-α/ß in regulation of ferroptosis and AKI. EXPERIMENTAL APPROACH: AKI model was established by treating mice with folic acid. Regulatory effects of Rev-erb-α/ß on AKI and ferroptosis were determined using single-gene knockout (Rev-erb-α-/- and Rev-erb-ß-/- ) mice, incomplete double-knockout (icDKO, Rev-erb-α+/- Rev-erb-ß-/- ) mice and cells with erastin-induced ferroptosis. Targeted antagonism of Rev-erb-α/ß to alleviate AKI and ferroptosis was assessed using the small-molecule antagonist SR8278. Transcriptional gene regulation was investigated using luciferase reporter, mobility shift and chromatin immunoprecipitation assays. KEY RESULTS: Loss of Rev-erb-α or Rev-erb-ß reduced the sensitivity of mice to folic acid-induced AKI and eliminated the circadian time dependency in disease severity. This coincided with less extensive ferroptosis, a main cause of folic acid-induced AKI. Moreover, icDKO mice were more resistant to folic acid-induced AKI and ferroptosis as compared with single-gene knockout mice. Supporting this, targeting Rev-erb-α/ß by SR8278 attenuated ferroptosis to ameliorate folic acid-induced AKI in mice. Rev-erb-α/ß promoted ferroptosis by repressing the transcription of Slc7a11 and HO1 (two ferroptosis-inhibitory genes) via direct binding to a RORE cis-element. CONCLUSION AND IMPLICATIONS: Targeted inhibition of Rev-erb-α/ß limits ferroptosis to ameliorate folic acid-induced AKI in mice. The findings may have implications for improved understanding of circadian clock-controlled ferroptosis and for formulating new strategies to treat AKI.


Asunto(s)
Lesión Renal Aguda , Ferroptosis , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Animales , Ritmo Circadiano , Ácido Fólico , Ratones , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/genética
13.
Sci Rep ; 10(1): 13114, 2020 08 04.
Artículo en Inglés | MEDLINE | ID: mdl-32753586

RESUMEN

Kernel water content (KWC) and kernel dehydration rate (KDR) are two main factors affecting maize seed quality and have a decisive influence on the mechanical harvest. It is of great importance to map and mine candidate genes related to KWCs and KDRs before physiological maturity in maize. 120 double-haploid (DH) lines constructed from Si287 with low KWC and JiA512 with high KWC were used as the mapping population. KWCs were measured every 5 days from 10 to 40 days after pollination, and KDRs were calculated. A total of 1702 SNP markers were used to construct a linkage map, with a total length of 1,309.02 cM and an average map distance of 0.77 cM. 10 quantitative trait loci (QTLs) and 27 quantitative trait nucleotides (QTNs) were detected by genome-wide composite interval mapping (GCIM) and multi-locus random-SNP-effect mixed linear model (mrMLM), respectively. One and two QTL hotspot regions were found on Chromosome 3 and 7, respectively. Analysis of the Gene Ontology showed that 2 GO terms of biological processes (BP) were significantly enriched (P ≤ 0.05) and 6 candidate genes were obtained. This study provides theoretical support for marker-assisted breeding of mechanical harvest variety in maize.


Asunto(s)
Mapeo Cromosómico , Estudio de Asociación del Genoma Completo , Sitios de Carácter Cuantitativo/genética , Agua/metabolismo , Zea mays/genética , Zea mays/metabolismo , Haploidia , Fenotipo , Polimorfismo de Nucleótido Simple
14.
Biochem Pharmacol ; 178: 114045, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32446886

RESUMEN

Dosing time accounts for a large variability in efficacy and/or toxicity for many drugs. Therefore, chronotherapy has been shown to effectively improve drug efficacy and to reduce drug toxicity. Circadian changes in pharmacokinetics and pharmacodynamics (drug target) are two essential sources of time-varying drug effects. Pharmacokinetics determines the drug and metabolite concentrations (exposure) in target tissues/organs, thereby impacting drug efficacy and toxicity. Pharmacokinetic processes are generally divided into drug absorption, distribution, metabolism and excretion (so-called "ADME"). Recent years of studies have revealed circadian (~24 h) rhythms in ADME processes, and clarified the underlying mechanisms related to circadian clock regulation. Furthermore, there is accumulating evidence that circadian pharmacokinetics can be translated to chronotoxicity and chronoefficacy. In this article, we review circadian rhythms in pharmacokinetic behaviors along with the underlying mechanisms. We also discuss the correlations of circadian pharmacokinetics with chronotoxicity and chronoefficacy.


Asunto(s)
Cronoterapia/métodos , Ritmo Circadiano/efectos de los fármacos , Ritmo Circadiano/fisiología , Preparaciones Farmacéuticas/metabolismo , Animales , Relojes Circadianos/efectos de los fármacos , Relojes Circadianos/fisiología , Humanos , Preparaciones Farmacéuticas/administración & dosificación , Distribución Tisular/efectos de los fármacos , Distribución Tisular/fisiología
15.
Int J Biol Macromol ; 159: 304-315, 2020 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-32422262

RESUMEN

Massive blood loss and bacterial infection are major challenges for global public health. However, traditional wound dressings cannot fully meet the current clinical needs in controlling bleeding and avoiding infection. In this study, we prepared a chitin nanofiber suspension by green mechanical grinding and homogenizing, which could be used for developing a porous chitin nanofiber sponge by freeze drying. Then tannic acid/CaII was anchored on the surface of chitin nanofiber sponge by layer-by-layer deposition based on the coordination complex of tannic acid and Ca2+. These porous chitin nanofiber sponges with meso-macroporous structure could accelerate platelet aggregation for hemostasis. Hemostasis tests also demonstrated that the Ca2+ and TA in the TA/CaII coating on chitin nanofiber sponge could accelerate platelet activity and shorten the hemostatic time both in vitro and in vivo. Besides, the TA in the TA/CaII coating enhanced the antibacterial properties of the sponge, which depended the content of TA/CaII. Based on these results, it could be inferred that the chitin nanofiber sponges anchored TA/CaII coating had rapid hemostatic and antibacterial properties, which would have great potential for designing hemostatic product in clinical application.


Asunto(s)
Antibacterianos/química , Calcio/química , Quitina/química , Hemostáticos/química , Nanofibras/química , Taninos/química , Animales , Antibacterianos/farmacología , Pruebas de Coagulación Sanguínea , Línea Celular , Hemostasis/efectos de los fármacos , Hemostáticos/farmacología , Fenómenos Mecánicos , Ratones , Nanofibras/ultraestructura , Porosidad , Ratas , Espectroscopía Infrarroja por Transformada de Fourier , Propiedades de Superficie , Tapones Quirúrgicos de Gaza , Termogravimetría , Difracción de Rayos X
16.
Plant Sci ; 292: 110380, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32005385

RESUMEN

Water deficits are a major constraint on maize growth and yield, and deep roots are one of the major mechanisms of drought tolerance. In this study, four root and shoot traits were evaluated within an association panel consisting of 209 diverse maize accessions under well-watered (WW) and water-stressed (WS) conditions. A significant positive correlation was observed between seminal root length (SRL) under WS treatment and the drought tolerance index (DI) of maize seedlings. The transcriptome profiles of maize seminal roots were compared between four drought-tolerant lines and four drought-sensitive lines under both water conditions to identify genes associated with the drought stress response. After drought stress, 343 and 177 common differentially expressed genes (DEGs) were identified in the drought-tolerant group and drought-sensitive group, respectively. In parallel, a coexpression network underlying SRL was constructed on the basis of transcriptome data, and 10 hub genes involved in two significant associated modules were identified. Additionally, a genome-wide association study (GWAS) of the SRL revealed 62 loci for the two water treatments. By integrating the results of the GWAS, the common DEGs and the coexpression network analysis, 7 promising candidate genes were prioritized for further research. Together, our results provide a foundation for the enhanced understanding of seminal root changes in response to drought stress in maize.


Asunto(s)
Sequías , Genes de Plantas , Estudio de Asociación del Genoma Completo , Transcriptoma , Zea mays/genética , Raíces de Plantas/genética , Raíces de Plantas/crecimiento & desarrollo , Plantones/genética , Plantones/crecimiento & desarrollo , Estrés Fisiológico , Zea mays/crecimiento & desarrollo
17.
Plant Physiol Biochem ; 145: 174-183, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31704591

RESUMEN

Drought significantly affects plant growth and has devastating effects on crop production, NAC transcription factors respond to abiotic stresses by activating gene expression. In this study, a maize NAC transcription factor, ZmNAC33, was cloned and characterized its function in Arabidopsis. Transient transformation in Arabidopsis leaves mesophyll protoplasts and trans-activation assays in yeast showed that ZmNAC33 was localized in the nucleus and had transactivation activity. qRT-PCR analysis showed that ZmNAC33 in maize was induced by drought, high salinity and abscisic acid (ABA) stress. Promoter analysis identified multiple stress-related cis-acting elements in the promoter region of ZmNAC33. In ZmNAC33 transgenic Arabidopsis, germination rates were higher than in wild type plants under ABA and osmotic stress at the germination stage, and overexpression lines exhibited higher survival rates and higher antioxidant enzyme activities compared with wild type under drought stress. These results indicate that ZmNAC33 actes as a positive regulator in drought tolerance in plants.


Asunto(s)
Arabidopsis , Sequías , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Estrés Fisiológico , Factores de Transcripción , Arabidopsis/genética , Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/metabolismo , Estrés Fisiológico/genética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo
18.
Front Chem ; 7: 636, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31620429

RESUMEN

b-oriented ZSM-5 zeolite film was synthesized on the macropore α-quartz substrate modified with titanium dioxide (TiO2), polyvinyl acetate (PVA), and chitosan (CTS) by hydrothermal crystallization. By comparing the binding energy and b-oriented angle of zeolite film on each modified α-quartz substrate, the orientations, and combinations derived from structure-adsorption relationship were investigated with Material Studio simulation. Furthermore, the effects of calcination temperature and ultraviolet (UV) irradiation time on the surface structure and adsorption activity of TiO2 coating were studied. The increase adsorption potential energy and the formation of Ti-O-Si bind between zeolite crystal phase and substrate facilitate the continuous and uniform zeolite film growth. The TiO2 interlayer with anatase phase after UV irradiation presents a smooth surface with high Ti-OH density, consequently to high selectivity of b-orientation growth for the ZSM-5 crystals. Compared with the traditional ZSM-5, the higher stability has been exhibited with b-oriented ZSM-5 film /TiO2/α-quartz in the MTA reaction, and the methanol conversion and BTX selectivity remained higher than 90 and 70%, after 6 h reaction.

19.
Plant Cell Rep ; 37(2): 251-264, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29098377

RESUMEN

KEY MESSAGE: This work provides the bioinformatics, expression pattern and functional analyses of cryptochrome 1a from sweet sorghum (SbCRY1a), together with an exploration of the signaling mechanism mediated by SbCRY1a. Sweet sorghum [Sorghum bicolor (L.) Moench] is considered to be an ideal candidate for biofuel production due to its high efficiency of photosynthesis and the ability to maintain yield under harsh environmental conditions. Blue light receptor cryptochromes regulate multiple aspects of plant growth and development. Here, we reported the function and signal mechanism of sweet sorghum cryptochrome 1a (SbCRY1a) to explore its potential for genetic improvement of sweet sorghum varieties. SbCRY1a transcripts experienced almost 24 h diurnal cycling; however, its protein abundance showed no oscillation. Overexpression of SbCRY1a in Arabidopsis rescued the phenotype of cry1 mutant in a blue light-specific manner and regulated HY5 accumulation under blue light. SbCRY1a protein was present in both nucleus and cytoplasm. The photoexcited SbCRY1a interacted directly with a putative RING E3 ubiquitin ligase constitutive photomorphogenesis 1 (COP1) from sweet sorghum (SbCOP1) instead of SbSPA1 to suppress SbCOP1-SbHY5 interaction responding to blue light. These observations indicate that the function and signaling mechanism of cryptochromes are basically conservative between monocotyledons and dicotyledons. Moreover, SbCRY1a-overexpressed transgenic Arabidopsis showed oversensitive to abscisic acid (ABA) and salinity. The ABA-responsive gene ABI5 was up-regulated evidently in SbCRY1a transgenic lines, suggesting that SbCRY1a might regulate ABA signaling through the HY5-ABI5 regulon.


Asunto(s)
Ácido Abscísico/farmacología , Arabidopsis/genética , Criptocromos/genética , Regulación de la Expresión Génica de las Plantas/genética , Luz , Sorghum/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Criptocromos/metabolismo , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas/efectos de la radiación , Mutación , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Reguladores del Crecimiento de las Plantas/farmacología , Plantas Modificadas Genéticamente , Salinidad
20.
Oncol Lett ; 15(1): 552-558, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29285200

RESUMEN

The present study aimed to identify the level of programmed death-1 (PD-1) expression in infiltrating cluster of differentiation (CD)4+ and CD8+ T cells isolated from lung cancer tissues, and investigated whether the level of PD-1 expression may be directly regulated by lung cancer cells via prostaglandin E2 (PGE2)-associated signaling pathways in patients with lung cancer. A total of 75 patients with lung cancer were enrolled in the present study. The percentage of infiltrating CD4+ and CD8+ T cells was determined by flow cytometry. ELISA was performed to evaluate the concentration of PGE2 in lung cancer tissue homogenate. The correlation between PGE2 and PD-1 expression levels in CD8+ T cells was assessed by Spearman's rank correlation test. The expression levels of PD-1 and PGE2 receptors were determined by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The level of PD-1 expression in infiltrating CD8+ T cells was gradually increased as the stage of lung cancer increased. The level of PD-1 expression was also positively associated with the concentration of PGE2 in lung cancer tissues. Furthermore, the level of PD-1 expression was closely associated with the PGE2/EP2 and PGE2/EP4 signaling pathways. The activation of PGE2-associated EP2- and EP4-pathways may positively regulate the level of PD-1 in infiltrating CD8+ T cells, which results in immune tolerance in the lung cancer microenvironment.

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