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1.
Biomater Sci ; 12(10): 2639-2647, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38563394

RESUMEN

Triple negative breast cancer (TNBC) exhibits limited responsiveness to immunotherapy owing to its immunosuppressive tumor microenvironment (TME). Here, a reactive oxygen species (ROS)-labile nanodrug encapsulating the photosensitizer Ce6 and Bcl-2 inhibitor ABT-737 was developed to provoke a robust immune response via the synergistic effect of photodynamic therapy (PDT) and the reversal of apoptosis resistance. Upon exposure to first-wave near-infrared laser irradiation, the generated ROS triggers PEG cleavage, facilitating the accumulation of the nanodrug at tumor region and endocytosis by tumor cells. Further irradiation leads to the substantial generation of cytotoxic ROS, initiating an immunogenic cell death (ICD) cascade, which prompts the maturation of dendritic cells (DCs) as well as the infiltration of T cells into the tumor site. Meanwhile, Bcl-2 inhibition counteracts apoptosis resistance, thereby amplifying PDT-induced ICD and bolstering antitumor immunity. As a result, the ROS-sensitive nanodrug demonstrates a potent inhibitory effect on tumor growth.


Asunto(s)
Apoptosis , Compuestos de Bifenilo , Inmunoterapia , Fotoquimioterapia , Fármacos Fotosensibilizantes , Especies Reactivas de Oxígeno , Sulfonamidas , Neoplasias de la Mama Triple Negativas , Neoplasias de la Mama Triple Negativas/terapia , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/inmunología , Humanos , Apoptosis/efectos de los fármacos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/administración & dosificación , Femenino , Especies Reactivas de Oxígeno/metabolismo , Animales , Ratones , Compuestos de Bifenilo/farmacología , Compuestos de Bifenilo/química , Sulfonamidas/farmacología , Sulfonamidas/química , Clorofilidas , Línea Celular Tumoral , Piperazinas/farmacología , Piperazinas/química , Nitrofenoles/farmacología , Nitrofenoles/química , Nanopartículas/química , Porfirinas/farmacología , Porfirinas/química , Antineoplásicos/farmacología , Antineoplásicos/química
2.
Sci Rep ; 14(1): 5959, 2024 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-38472335

RESUMEN

In recent years, human umbilical cord mesenchymal stem cell (hUC-MSC) extracellular vesicles (EVs) have been used as a cell replacement therapy and have been shown to effectively overcome some of the disadvantages of cell therapy. However, the specific mechanism of action of EVs is still unclear, and there is no appropriate system for characterizing the differences in the molecular active substances of EVs produced by cells in different physiological states. We used a data-independent acquisition (DIA) quantitative proteomics method to identify and quantify the protein composition of two generations EVs from three different donors and analysed the function and possible mechanism of action of the proteins in EVs of hUC-MSCs via bioinformatics. By comparative proteomic analysis, we characterized the different passages EVs. Furthermore, we found that adaptor-related protein complex 2 subunit alpha 1 (AP2A1) and adaptor-related protein complex 2 subunit beta 1 (AP2B1) in hUC-MSC-derived EVs may play a significant role in the treatment of Alzheimer's disease (AD) by regulating the synaptic vesicle cycle signalling pathway. Our work provides a direction for batch-to-batch quality control of hUC-MSC-derived EVs and their application in AD treatment.


Asunto(s)
Enfermedad de Alzheimer , Vesículas Extracelulares , Células Madre Mesenquimatosas , Humanos , Enfermedad de Alzheimer/metabolismo , Proteómica , Complejo 2 de Proteína Adaptadora/metabolismo , Vesículas Extracelulares/metabolismo
3.
ACS Appl Mater Interfaces ; 16(4): 4863-4872, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38237116

RESUMEN

A butterfly-shaped phenothiazine derivative, PTTCN, was synthesized to obtain pure organic porous crystals for the highly efficient absorptive separation of toluene (Tol) and methylcyclohexane (Mcy). Due to the presence of three polar cyano groups and nonplanar conformation, these molecules self-assembled into a hydrogen-bonded organic framework (X-HOF-5) with distinct cavities capable of accommodating Tol molecules through multiple hydrogen-bonding interactions. Upon solvent removal via heating, the activated X-HOF-5 retained its cavity structure albeit with altered stacking arrangements, accompanied by a remarkable fluorescent color change from cyan to green. X-HOF-5a can undergo a phase transformation into X-HOF-5 upon reabsorption of Tol, while exhibiting no accommodation of Mcy due to the weak intermolecular interaction between PTTCN and Mcy. This suggests that the activated HOF material prefers Tol over Mcy. Moreover, X-HOF-5a may selectively accommodate Tol in a Tol/Mcy equimolar mixture, and the purity of Tol can reach 97% after release from the framework. Additionally, it is noteworthy that the HOF material exhibits recyclability without any discernible loss in performance.

4.
Acta Biomater ; 170: 215-227, 2023 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-37619897

RESUMEN

Abnormally high level of cell-free DNA (cfDNA) is one of the important causes of autoimmune diseases, which aggravate the symptoms of rheumatoid arthritis (RA). Recently, the utilization of cationic polymeric nanoparticles for scavenging cfDNA has emerged as a promising therapeutic strategy for the treatment of RA. However, the intravenous introduction of cationic polymeric nanoparticles into the circulation carries a risk of dissociation, causing toxicity. To realize the potential clinical translation, we employed a series of silica particles grafted with poly(2-(dimethylamino) ethyl methacrylate) (PDMA) (SiNP@PDMA) brush, which possess adjustable PDMA content (100, 200, and 300 degree of polymerization (DP)) and particle size (50, 100, and 200 nm diameter), to selectively scavenge cfDNA in inflamed joint cavity. We demonstrate that the binding affinity for cfDNA, cytotoxicity, circulation time in vivo and retention in the inflamed joint cavity are influenced by the core-shell structure of SiNP@PDMA, ultimately impacting therapeutic efficacy. Among them, SiNP@PDMA with 100 nm size and 200 DP of PDMA exhibit enhanced accumulation and prolonged retention time in inflammatory joint cavity, resulting in superior therapeutic effect. Therefore, in this study, applying the precisely tuning size and cation content of SiNP@PDMA, we demonstrated the factors to matter the therapeutic effect of cationic nanoparticles, which deepened the understanding of the anti-inflammatory therapies based on cfDNA scavenger for RA. STATEMENT OF SIGNIFICANCE: Inspired by the discovery that cfDNA would induce inappropriate immune responses to exacerbate the progress of RA, we innovatively employed SiNP@PDMA as a cfDNA scavenger to inhibit cfDNA-induced inflammation in RA. Increase in the cation content efficiently strengthened the binding between SiNP@PDMA and cfDNA, leading to an improvement in inhibitory effect of inflammation. In addition, we compared the behaviors of 50, 100 and 200 nm SiNP@PDMA in RA symptom suppression, local cfDNA scavenging and inflammation inhibition. The results demonstrated that SiNP100-PDMA200 outperformed other analogues, corresponding to their more favorable distribution in inflammatory articular cavity. Together, this study revealed the structure-property relationship of cfDNA scavengers for further development of safe and effective cfDNA scavenging system.

5.
Small ; 19(42): e2304340, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37323072

RESUMEN

A nonplanar phenothiazine derivative with three cyano moieties (PTTCN) is designed and synthesized to achieve functional crystals for absorptive separation of benzene and cyclohexane. PTTCN can crystallize into two kinds of crystals with different fluorescence colors in different solvent systems. The molecules in two crystals are in different stereo isomeric forms of nitrogen, quasi axial (ax), and quasi equatorial (eq). The crystals with blue fluorescence in ax form may selectively adsorb benzene by a single-crystal-to-single-crystal (SCSC) transformation, but separated benzene from a benzene/cyclohexane equimolar mixture with a low purity of 79.6%. Interestingly, PTTCN molecules with eq form and benzene co-assembled to construct a hydrogen-bonded framework (X-HOF-4) with S-type solvent channels and yellow-green fluorescence, and can release benzene to form nonporous guest-free crystal under heating. Such nonporous crystals strongly favor aromatic benzene over cyclohexane and may selectively reabsorb benzene from benzene/cyclohexane equimolar mixture to recover original framework, and the purity of benzene can reach ≈96.5% after release from framework. Moreover, reversible transformation between the nonporous crystals and the guest-containing crystals allows the material to be reused.

6.
J Cereb Blood Flow Metab ; 43(10): 1702-1712, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37021629

RESUMEN

Finding appropriate drugs to improve cerebral autoregulation (CA) in patients with acute ischemic stroke (AIS) is necessary to improve prognosis. We aimed to investigate the effect of butylphthalide on CA in patients with AIS. In this randomized controlled trial, 99 patients were 2:1 randomized to butylphthalide or placebo group. The butylphthalide group received intravenous infusion with a preconfigured butylphthalide-sodium chloride solution for 14 days and an oral butylphthalide capsule for additional 76 days. The placebo group synchronously received an intravenous infusion of 100 mL 0.9% saline and an oral butylphthalide simulation capsule. The transfer function parameter, phase difference (PD), and gain were used to quantify CA. The primary outcomes were CA levels on the affected side on day 14 and day 90. Eighty patients completed the follow-up (52 in the butylphthalide group and 28 in the placebo group). The PD of the affected side on 14 days or discharge and on 90 days was higher in the butylphthalide group than in the placebo group. The differences in safety outcomes were not significant. Therefore, butylphthalide treatment for 90 days can significantly improve CA in patients with AIS.Trial registration: ClinicalTrial.gov: NCT03413202.


Asunto(s)
Aterosclerosis , Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Arterias , Homeostasis , Accidente Cerebrovascular/tratamiento farmacológico , Resultado del Tratamiento , Isquemia Encefálica/tratamiento farmacológico
7.
Front Cell Neurosci ; 16: 998512, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36439197

RESUMEN

Background: 4-Hydroxynonenal (4-HNE), an α, ß-unsaturated hydroxyalkenal, has been found to be associated with aspirin resistance, which is a risk factor for recurrent cerebral infarction. However, its effect on recurrent cerebral infarction is less defined. We designed this study to investigate the association between 4-HNE and increased risk of recurrent cerebral infarction. Methods: We recruited 189 patients with primary cerebral infarction from 2017 to 2019. According to the recurrence of cerebral infarction during the 3-year follow-up period, they were divided into two groups, namely, the non-recurrence group (n = 93) and the recurrence group (n = 96). All patients were analyzed to explore the risk factors for the recurrence of primary cerebral infarction and the predictive value of serum 4-HNE for the recurrence of cerebral infarction. Results: The levels of serum 4-HNE in patients of the recurrence group were significantly higher than that in patients of the non-recurrence group. There was a positive correlation between serum 4-HNE levels and the serum levels of triglyceride (r = 0.448, p = 0.008) and low-density lipoprotein cholesterol (LDL-C; r = 0.442, p = 0.002) in primary cerebral infarction patients. Cox proportional hazards modeling showed that demographic and certain clinical parameters, such as age, serum triglyceride levels, the National Institutes of Health Stroke Scale (NIHSS) scores, and serum 4-HNE levels, were independent factors for the recurrence in patients. The results of the receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) value of serum 4-HNE in patients with cerebral infarction recurrence was 0.703, and when the cutoff value of serum 4-HNE was set at 42.34 ng/ml, the sensitivity and specificity values of serum 4-HNE in predicting recurrent cerebral infarction were 79.20 and 52.70%, respectively. Conclusion: Serum 4-HNE is an independent risk factor for the recurrence of patients with primary cerebral infarction, and it may become a new intervention way to prevent the recurrence of patients with cerebral infarction.

8.
Artículo en Inglés | MEDLINE | ID: mdl-36011573

RESUMEN

Many small-spacing interchanges (SSI) appear when the density of the expressway interchanges increases. However, the characteristics of traffic accidents in SSI have not been explained clearly. Therefore, this paper systematically takes the G3001 expressway in Xi'an as the research object to explore the accident characteristics of SSI. Firstly, the expressway is divided into four sections. Furthermore, their safety can be evaluated by the number of accidents per unit distance of 100 million vehicles (NAP). Subsequently, eight indexes, such as mean spacing distance (MSD), are selected to explain the cause affecting expressway safety by developing the least square support vector machine (LSSVM). Secondly, the difference between SSI and normal-spacing interchanges (NSI) is clarified by statistical analysis. Finally, LSSVM, random forest, and logistic regression models are built using 12 indicators, such as the time spent exploring the causes of serious accidents. The results show that the inner ring NAP in Sections I and II with SSI is 27.2 and 33.7, higher than in other sections. The density, annual average daily traffic, and MSD adversely affect expressway traffic safety. The road condition mainly influences the serious traffic accidents in the SSI. This study can provide the theoretical basis for traffic management and accident prevention in the SSI of the expressway.


Asunto(s)
Accidentes de Tránsito , Máquina de Vectores de Soporte , Modelos Logísticos , Factores de Riesgo
9.
Biomaterials ; 286: 121594, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35640491

RESUMEN

Abnormal high cell-free DNA (cfDNA) activates toll-like receptor 9 (TLR9) in immune cell's endosome to produce inflammatory cytokines that aggravate rheumatoid arthritis (RA). Previously, we successfully developed cationic nanoparticles (cNPs) relieving symptoms of RA rats by scavenging cfDNA, but the strong positive charges of cNPs may cause systemic toxicity during circulation via intravenous injection. Herein, we design cNP-pp-PEG to shield the nanoparticles with MMP2-sensitive peptide (pp) linked PEG, the cations are exposed only when PEG is removed by MMP2, which is enriched in the inflamed articular cavity. Taking advantage of the self-assembled cNP-pp-PEG, hydrophobic methotrexate (MTX) is loaded into its core through hydrophobicity interaction, obtaining MTX@cNP-pp-PEG. The engineered reagents exhibit lower toxicity, longer retention time and higher accumulation in inflamed joints comparing to its counterpart MTX@cNP-pp due to the hidden cationic charges. Moreover, the anti-inflamed activity of MTX strengthens the therapeutic efficiency of cNPs. The dual roles of cNPs as therapeutic agent and MTX carrier significantly enhance the therapeutic efficacy and extended administration interval to 4 days. This research addresses the issues of targeting inflamed joints, reducing the systemic toxicities of both cNPs and MTX, and extending administration interval, demonstrating an upgraded strategy for DNA scavenger application.


Asunto(s)
Antirreumáticos , Artritis Reumatoide , Ácidos Nucleicos Libres de Células , Animales , Artritis Reumatoide/tratamiento farmacológico , ADN/uso terapéutico , Inflamación/tratamiento farmacológico , Metaloproteinasa 2 de la Matriz , Metotrexato/farmacología , Metotrexato/uso terapéutico , Ratas
10.
PLoS One ; 17(3): e0264473, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35245305

RESUMEN

Evaluation of the passenger departure efficiency of a comprehensive transport hub is essential for traffic managers. Through the evaluation, security risks in the hub can be found in time to ensure the safe departure of passengers. The attention of existing studies has focused on the analysis of the overall situation of the hub, and the quantitative description of departure status in different connection areas inside the hub is insufficient. In this study, a multilayer hybrid model based on an analytic hierarchy process and entropy weight method was established. The data collected using Wi-Fi probe technology were clustered by a K-means algorithm. The first level of the model was divided according to the connection areas of the passenger hub, and the second level was based on the number of stranded people, wait time and departure time in each connection area. It was found that the SP index has the greatest impact on departure efficiency. In addition, the impact of passenger flow aggregation on each connection area is different, and the management department should treat it accordingly. The applicability of the proposed multilayer hybrid model was verified in the example of the Chongqing north railway station.


Asunto(s)
Algoritmos , Humanos
11.
Bioact Mater ; 13: 249-259, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35224306

RESUMEN

A central paradigm in nanomedicine is that when synthetic nanoparticles (NPs) enter the body, they are immediately cloaked by a corona of macromolecules (mostly proteins) that mediates the role of the physico-chemical properties in the NP biological functions (the "coronation paradigm"). In this work, we focused on the assessment of the "coronation paradigm" for cationic NPs (cNPs) used as rheumatoid arthritis (RA) drugs due to their ability to scavenge cell-free DNA (cfDNA). We fabricated series of cNPs uniformly coated with single or di-hydroxyl groups and different types of amino groups and showed that hydroxylated nanoparticles displayed a prolonged retention in inflamed joints and greater anti-inflammatory effect in collagen-induced arthritis (CIA) rats than the non-hydroxylated analogues. Especially, the cNPs with secondary amines and a di-hydroxyl shell showed the best performance among the tested cNPs. Proteomic analysis showed that the cNPs with a di-hydroxyl shell adsorbed less opsonin proteins than the cNPs carrying mono hydroxyl groups and non-hydroxylated ones, which may provide a mechanistic explanation for the different biodistribution profiles of cNPs. Thus, this study suggests that the protein corona mediates the effects of the surface chemistry on the fate and functions of cNPs as anti-RA drugs.

12.
Exp Dermatol ; 31(6): 906-917, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35119146

RESUMEN

Androgenetic alopecia (AGA) is a prevalent hair loss condition in males that develops due to the influence of androgens and genetic predisposition. With the aim of elucidating genes involved in AGA pathogenesis, we modelled AGA with three-dimensional culture of keratinocyte-surrounded dermal papilla (DP) cells. We co-cultured immortalised balding and non-balding human DP cells (DPCs) derived from male AGA patients with epidermal keratinocyte (NHEK) using multi-interfacial polyelectrolyte complexation technique. We observed up-regulated mitochondria-related gene expression in balding compared with non-balding DP aggregates which indicated altered mitochondria metabolism. Further observation of significantly reduced electron transport chain complex activity (complexes I, IV and V), ATP levels and ability to uptake metabolites for ATP generation demonstrated compromised mitochondria function in balding DPC. Balding DP was also found to be under significantly higher oxidative stress than non-balding DP. Our experiments suggest that application of antioxidants lowers oxidative stress levels and improves metabolite uptake in balding DPC. We postulate that the observed up-regulation of mitochondria-related genes in balding DP aggregates resulted from an over-compensatory effort to rescue decreased mitochondrial function in balding DP through the attempted production of new functional mitochondria. In all, our three-dimensional co-culturing revealed mitochondrial dysfunction in balding DPC, suggesting a metabolic component in the aetiology of AGA.


Asunto(s)
Alopecia , Andrógenos , Adenosina Trifosfato/metabolismo , Alopecia/patología , Andrógenos/metabolismo , Folículo Piloso/metabolismo , Humanos , Queratinocitos/metabolismo , Masculino , Mitocondrias/metabolismo
13.
CNS Neurosci Ther ; 28(2): 298-306, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34894087

RESUMEN

AIMS: Cerebral small vessel disease (CSVD) is characterized by functional and structural changes in small vessels. We aimed to elucidate the relationship between dynamic cerebral autoregulation (dCA) and neuroimaging characteristics of CSVD. METHODS: A case-control study was performed. Cerebral blood flow velocity (CBFV) of bilateral middle cerebral arteries and spontaneous arterial blood pressure were simultaneously recorded. Transfer function analysis was used to calculate dCA parameters (phase, gain, and the rate of recovery of CBFV [RoRc]). Neuroimaging characteristics of CSVD patients were evaluated, including lacunes, white matter hyperintensities (WMH), cerebral microbleeds (CMBs), perivascular spaces (PVS), and the total CSVD burden. RESULTS: Overall, 113 patients and 83 controls were enrolled. Compared with the control group, the phase at low frequency and the RoRc in CSVD patients were lower, and the gain at very low and low frequencies were higher, indicating bilaterally impaired dCA. Total CSVD burden, WMH (total, periventricular and deep), severe PVS, and lobar CMBs were independently correlated with the phase at low frequency. CONCLUSIONS: Our findings suggested that dCA was compromised in CSVD patients, and some specific neuroimaging characteristics (the total CSVD burden, WMH, severe PVS and lobar CMBs) might indicate more severe dCA impairment in CSVD patients.


Asunto(s)
Enfermedades de los Pequeños Vasos Cerebrales/patología , Enfermedades de los Pequeños Vasos Cerebrales/fisiopatología , Circulación Cerebrovascular/fisiología , Homeostasis/fisiología , Neuroimagen , Sustancia Blanca/patología , Adulto , Anciano , Estudios de Casos y Controles , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Gravedad del Paciente , Sustancia Blanca/diagnóstico por imagen
14.
Front Oncol ; 11: 698551, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34336686

RESUMEN

INTRODUCTION: Circulating tumor cells (CTCs) and cell-free tumor DNA (ctDNA) are tumor components present in circulation. Due to the limited access to both CTC enrichment platforms and ctDNA sequencing in most laboratories, they are rarely analyzed together. METHODS: Concurrent isolation of ctDNA and single CTCs were isolated from lung cancer and breast cancer patients using the combination of size-based and CD45-negative selection method via DropCell platform. We performed targeted amplicon sequencing to evaluate the genomic heterogeneity of CTCs and ctDNA in lung cancer and breast cancer patients. RESULTS: Higher degrees of genomic heterogeneity were observed in CTCs as compared to ctDNA. Several shared alterations present in CTCs and ctDNA were undetected in the primary tumor, highlighting the intra-tumoral heterogeneity of tumor components that were shed into systemic circulation. Accordingly, CTCs and ctDNA displayed higher degree of concordance with the metastatic tumor than the primary tumor. The alterations detected in circulation correlated with worse survival outcome for both lung and breast cancer patients emphasizing the impact of the metastatic phenotype. Notably, evolving genetic signatures were detected in the CTCs and ctDNA samples during the course of treatment and disease progression. CONCLUSIONS: A standardized sample processing and data analysis workflow for concurrent analysis of CTCs and ctDNA successfully dissected the heterogeneity of metastatic tumor in circulation as well as the progressive genomic changes that may potentially guide the selection of appropriate therapy against evolving tumor clonality.

15.
Biomaterials ; 276: 121027, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34293700

RESUMEN

Abnormal high level of cell free DNA (cfDNA) triggers chronic inflammation to exacerbate psoriasis symptoms. Scavenging cfDNA by topical cationic polymeric nanoparticles has been certified as an effective therapeutic strategy for treating psoriasis. However, cationic cfDNA scavengers have a great potential risk to organs after entering systemic circulation through skin barrier. For better transformation to clinical application, herein a series of poly(2-(dimethylamino)ethyl methacrylate) (PDMA) grafted hairy silica particles (cSPs) with tunable PDMA length and particle size are applied to scavenge cfDNA in dermis. We reveal that the structure of cSPs correlates with the permeation ability across stratum corneum, retention time in dermis, binding affinity to cfDNA, and toxicity tolerance, which in turn affect the therapeutic effect. Especially, the cSPs of 700 nm show more accumulation and longer retention in psoriatic lesions, leading to excellent treatment results. They also outperform the cSPs of 200 nm at a lower administration frequency. Thus, we address the issues of size, cationic content of cSPs to open a potential new avenue to topically treatment of psoriasis by targeting cfDNA in dermis.


Asunto(s)
Ácidos Nucleicos Libres de Células , Nanopartículas , Psoriasis , Dermis , Humanos , Polímeros , Psoriasis/tratamiento farmacológico , Piel
16.
Ecol Evol ; 11(10): 5281-5294, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34026006

RESUMEN

Ectomycorrhizal (ECM) symbiosis is an evolutionary biological trait of higher plants for effective nutrient uptakes. However, little is known that how the formation and morphological differentiations of ECM roots mediate the nutrients of below- and aboveground plant tissues and the balance among nutrient elements across environmental gradients. Here, we investigated the effects of ECM foraging strategies on root and foliar N and P concentrations and N:P ratio Abies faxoniana under variations of climate and soil conditions.The ECM symbionts preferentially mediated P uptake under both N and P limitations. The uptake efficiency of N and P was primarily associated with the ECM root traits, for example, ECM root tip density, superficial area of ECM root tips, and the ratio of living to dead root tips, and was affected by the ECM proliferations and morphological differentiations. The tissue N and P concentrations were positively associated with the abundance of the contact exploration type and negatively with that of the short-distance exploration type.Our findings indicate that the nutritional status of both below- and aboveground plant tissues can be strongly affected by ECM symbiosis in natural environments. Variations in the ECM strategies in response to varying environmental conditions significantly influence plant nutrient uptakes and trade-offs.

17.
Blood ; 135(26): 2337-2353, 2020 06 25.
Artículo en Inglés | MEDLINE | ID: mdl-32157296

RESUMEN

Targeted therapies against the BCR-ABL1 kinase have revolutionized treatment of chronic phase (CP) chronic myeloid leukemia (CML). In contrast, management of blast crisis (BC) CML remains challenging because BC cells acquire complex molecular alterations that confer stemness features to progenitor populations and resistance to BCR-ABL1 tyrosine kinase inhibitors. Comprehensive models of BC transformation have proved elusive because of the rarity and genetic heterogeneity of BC, but are important for developing biomarkers predicting BC progression and effective therapies. To better understand BC, we performed an integrated multiomics analysis of 74 CP and BC samples using whole-genome and exome sequencing, transcriptome and methylome profiling, and chromatin immunoprecipitation followed by high-throughput sequencing. Employing pathway-based analysis, we found the BC genome was significantly enriched for mutations affecting components of the polycomb repressive complex (PRC) pathway. While transcriptomically, BC progenitors were enriched and depleted for PRC1- and PRC2-related gene sets respectively. By integrating our data sets, we determined that BC progenitors undergo PRC-driven epigenetic reprogramming toward a convergent transcriptomic state. Specifically, PRC2 directs BC DNA hypermethylation, which in turn silences key genes involved in myeloid differentiation and tumor suppressor function via so-called epigenetic switching, whereas PRC1 represses an overlapping and distinct set of genes, including novel BC tumor suppressors. On the basis of these observations, we developed an integrated model of BC that facilitated the identification of combinatorial therapies capable of reversing BC reprogramming (decitabine+PRC1 inhibitors), novel PRC-silenced tumor suppressor genes (NR4A2), and gene expression signatures predictive of disease progression and drug resistance in CP.


Asunto(s)
Crisis Blástica/genética , Regulación Leucémica de la Expresión Génica/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Complejo Represivo Polycomb 1/fisiología , Complejo Represivo Polycomb 2/fisiología , Diferenciación Celular , Inmunoprecipitación de Cromatina , Metilación de ADN , Conjuntos de Datos como Asunto , Proteína Potenciadora del Homólogo Zeste 2/fisiología , Dosificación de Gen , Ontología de Genes , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Mutación , Complejo Represivo Polycomb 1/genética , Complejo Represivo Polycomb 2/genética , Transcriptoma , Secuenciación del Exoma , Secuenciación Completa del Genoma
18.
RSC Adv ; 10(20): 12025-12034, 2020 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-35496621

RESUMEN

One D-A type cruciform luminophore MDCS-BC based on carbazole has been prepared. We observed that this compound exhibits unique intramolecular charge-transfer (ICT) and typical aggregation-induced enhanced emission (AIEE) properties with the solid-state luminescence efficiency of 0.184. Moreover, this luminophore shows a significant stimuli-induced emission enhancement and chromism effect with good reversibility. Upon grinding, the fluorescence color of the as-prepared samples can change from blue (454 nm) to green (504 nm). What is unexpected is that the fluorescence efficiency of the initial powder is dramatically increased from 0.184 to 0.424 upon grinding. The results of PXRD, DSC and spectral properties studies show that the mechanical force-induced luminescence enhancement and chromism behavior of MDCS-BC originates from the transition between crystal and amorphous morphology, and the large red-shift and the emission enhancement inducing by grinding may be attributed to the planarization of the molecular conformation and subsequent planar ICT process.

19.
Sensors (Basel) ; 19(14)2019 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-31323887

RESUMEN

Totally water-soluble N-doped Carbon dots (N-CDs) were synthesized by a green hydrothermal method from biomass using Highland barley as a carbon source and ethanediamine as nitrogen source. TEM and XRD showed the graphitic amorphous structure and narrow diameter distribution of these N-CDs. N-doping to the crystal lattice and carrying many hydrophilic groups on the surface of N-CDs were verified by XPS and FT-IR. The as-synthesized N-CDs emitted strong blue fluorescence at 480 nm and owned a relatively high quantum yield of 14.4%. The product also could sensitively and selectively detect Hg2+ ions in the range of 10-160 µM and the limit of detection was equal to 0.48 µM.


Asunto(s)
Técnicas Biosensibles , Mercurio/aislamiento & purificación , Puntos Cuánticos/química , Biomasa , Carbono/química , Colorantes Fluorescentes/química , Hordeum/química , Nitrógeno/química , Espectroscopía Infrarroja por Transformada de Fourier , Agua/química
20.
Sci Total Environ ; 622-623: 1463-1475, 2018 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-29890611

RESUMEN

Elevation is a complex environmental factor altering temperature, light, moisture and soil nutrient availability, and thus may affect plant growth and physiology. Such effects of elevation may also depend on seasons. Along an elevational gradient of the Balang Mountain, southwestern China, we sampled soil and 2-year old leaves, 2-year old shoots, stem sapwood and fine roots (diameter<5mm) of Quercus aquifolioides at 2843, 2978, 3159, 3327, 3441 and 3589m a.s.l. in both summer and winter. In summer, the concentrations of tissue non-structural carbohydrates (NSC) did not decrease with increasing elevation, suggesting that the carbon supply is sufficient for plant growth at high altitude in the growing season. The concentration of NSC in fine roots decreased with elevation in winter, and the mean concentration of NSC across tissues in a whole plant showed no significant difference between the two sampling seasons, suggesting that the direction of NSC reallocation among plant tissues changed with season. During the growing season, NSC transferred from leaves to other tissues, and in winter NSC stored in roots transferred from roots to aboveground tissues. Available soil N increased with elevation, but total N concentrations in plant tissues did not show any clear elevational pattern. Both available soil P and total P concentrations in all plant tissues decreased with increasing elevation. Thus, tissue N:P ratio increased with elevation, suggesting that P may become a limiting element for plant growth at high elevation. The present study suggests that the upper limit of Q. aquifolioides on Balang Mountain may be co-determined by winter root NSC storage and P availability. Our results contribute to better understanding of the mechanisms for plants' upper limit formation.


Asunto(s)
Altitud , Monitoreo del Ambiente , Quercus/fisiología , Suelo/química , Carbohidratos , Carbono/análisis , China , Nitrógeno/análisis , Fósforo/análisis
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