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1.
Org Biomol Chem ; 22(13): 2566-2573, 2024 03 27.
Artículo en Inglés | MEDLINE | ID: mdl-38465392

RESUMEN

N 6-Methyladenosine (6mA) is a well-known prokaryotic DNA modification that has been shown to play epigenetic roles in eukaryotic DNA. Accurate detection and quantification of 6mA are prerequisites for molecular understanding of the impact of 6mA modification on DNA. However, the existing methods have several problems, such as high false-positive rate, time-consuming and complex operating procedures. Chemical sensors for the selective detection of 6mA modification are rarely reported in the literature. Fluorinated phenylboronic acid combined with 19F NMR analysis is an effective method for determining DNA or RNA modification. In this study, we presented a simple and fast chemical method for labelling the 6th imino group of 6mA using a boric-acid-derived probe. Besides, the trifluoromethyl group of trifluoromethyl phenylboronic acid (2a) could detect 6mA modification through 19F NMR. Combined with this sensor system, 6mA modification could be detected well and quickly in 6 types of deoxynucleoside mixtures and DNA samples. Taken together, the method developed in the current study has potential for specific detection of 6mA in biological samples.


Asunto(s)
Adenosina/análogos & derivados , Ácidos Borónicos , ADN , ADN/química , Metilación de ADN , Espectroscopía de Resonancia Magnética
2.
Orthop J Sports Med ; 12(2): 23259671231224497, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38343647

RESUMEN

Background: An accurate and objective criterion is needed to determine candidates who are suitable for hip arthroscopy in patients with femoroacetabular impingement (FAI). Purpose: To determine whether improvement in pain after ultrasound (US)-guided intra-articular hip injection during standardized examinations can be used to predict the outcomes of hip arthroscopy in patients with FAI. Study Design: Cohort study; Level of evidence, 3. Methods: We enrolled 119 patients with FAI who underwent US-guided intra-articular hip injection of local anesthesia during standardized examinations, carried out from May 2018 to February 2020 (within 2 weeks before hip arthroscopy). All patients had undergone a minimum of 6 months of nonoperative treatment without remission and had 2-year follow-up data. Pain visual analog scale (VAS) scores (0-10) were recorded for 7 different physical examination tests, and a total score (0 [best] to 70 [worst]) was obtained. In addition, International Hip Outcome Tool-12 (iHOT-12) and modified Harris Hip Score (mHHS) scores were recorded before hip arthroscopy and at final follow-up. According to whether patients achieved the substantial clinical benefit (SCB) on the iHOT-12, they were divided into SCB and non-SCB groups, and the improvement in VAS pain scores from preinjection to postinjection (ΔVAS pain) was compared between the 2 groups. Logistic regression analysis was used to predict the achievement of SCB, and the area under the receiver operating characteristic curve (AUC) was used to estimate the accuracy of the prediction. Results: There was a significant pre- to postoperative increase in iHOT-12 (31.6 points; P < .001) and mHHS (20.0 points; P < .001) scores, and 84 (70.6%) patients achieved the SCB. The ΔVAS pain score was significantly greater in the SCB versus the non-SCB group (16.0 vs 7.0 points; respectively; P < .001). Logistic regression analysis demonstrated an optimal cutoff value of 8.5 points for ΔVAS pain (AUC, 0.772; 95% CI, 0.687-0.858). For patients with more severe symptoms (total preinjection VAS pain score of >10 out of 70), the accuracy of the prediction for ΔVAS pain had a better evaluation value (AUC, 0.834; 95% CI, 0.676-0.992). Conclusion: Improvement in pain after US-guided intra-articular hip injection predicted the outcomes of hip arthroscopy in patients with FAI in this study, especially for patients with more severe pain.

3.
Exp Hematol Oncol ; 13(1): 20, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38388466

RESUMEN

BACKGROUND: Hepatocellular carcinoma (HCC) is closely associatedwith chronic liver diseases, particularly liver cirrhosis, which has an altered extracellular matrix (ECM) composition. The influence and its mechanism of the cirrhotic-ECM on the response of HCC to immune checkpoint inhibitor (ICI) remains less clarified. METHODS: In silico, proteomic and pathological assessment of alteration of cirrhotic-ECM were applied in clinical cohort. Multiple pre-clinical models with ECM manipulation were used to evaluate cirrhotic-ECM's effect on ICI treatment. In silico, flow cytometry and IHC were applied to explore how cirrhotic-ECM affect HCC microenvironment. In vitro and in vivo experiments were carried out to identify the mechanism of how cirrhotic-ECM undermined ICI treatment. RESULTS: We defined "a pro-tumor cirrhotic-ECM" which was featured as the up-regulation of collagen type 1 (Col1). Cirrhotic-ECM/Col1 was closely related to impaired T cell function and limited anti PD-1 (aPD-1) response of HCC patients from the TCGA pan cancer cohort and the authors' institution, as well as in multiple pre-clinical models. Mechanically, cirrhotic-ECM/Col1 orchestrated an immunosuppressive microenvironment (TME) by triggering Col1-DDR1-NFκB-CXCL8 axis, which initiated neutrophil extracellular traps (NETs) formation to shield HCC cells from attacking T cells and impede approaching T cells. Nilotinib, an inhibitor of DDR1, reversed the neutrophils/NETs dominant TME and efficiently enhanced the response of HCC to aPD-1. CONCLUSIONS: Cirrhotic-ECM modulated a NETs enriched TME in HCC, produced an immune suppressive TME and weakened ICI efficiency. Col1 receptor DDR1 could be a potential target synergically used with ICI to overcome ECM mediated ICI resistance. These provide a mechanical insight and novel strategy to overcome the ICI resistance of HCC.

4.
J Clin Apher ; 39(1): e22103, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38098278

RESUMEN

The purpose of this retrospective study is to compare the efficacy and safety of the centrifugal separation therapeutic plasma exchange (TPE) using citrate anticoagulant (cTPEc) with membrane separation TPE using heparin anticoagulant (mTPEh) in liver failure patients. The patients treated by cTPEc were defined as cTPEc group and those treated by mTPEh were defined as mTPEh group, respectively. Clinical characteristics were compared between the two groups. Survival analyses of two groups and subgroups classified by the model for end-stage liver disease (MELD) score were performed by Kaplan-Meier method and were compared by the log-rank test. In this study, there were 51 patients in cTPEc group and 18 patients in mTPEh group, respectively. The overall 28-day survival rate was 76% (39/51) in cTPEc group and 61% (11/18) in mTPEh group (P > .05). The 90-day survival rate was 69% (35/51) in cTPEc group and 50% (9/18) in mTPEh group (P > .05). MELD score = 30 was the best cut-off value to predict the prognosis of patients with liver failure treated with TPE, in mTPEh group as well as cTPEc group. The median of total calcium/ionized calcium ratio (2.84, range from 2.20 to 3.71) after cTPEc was significantly higher than the ratio (1.97, range from 1.73 to 3.19) before cTPEc (P < .001). However, there was no significant difference between the mean concentrations of total calcium before cTPEc and at 48 h after cTPEc. Our study concludes that there was no statistically significant difference in survival rate and complications between cTPEc and mTPEh groups. The liver failure patients tolerated cTPEc treatment via peripheral vascular access with the prognosis similar to mTPEh. The prognosis in patients with MELD score < 30 was better than in patients with MELD score ≥ 30 in both groups. In this study, the patients with acute liver failure (ALF) and acute on chronic liver failure (ACLF) treated with cTPEc tolerated the TPE frequency of every other day without significant clinical adverse event of hypocalcemia with similar outcomes to the mTPEh treatment. For liver failure patients treated with cTPEc, close clinical observation and monitoring ionized calcium are necessary to ensure the patients' safety.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada , Enfermedad Hepática en Estado Terminal , Humanos , Insuficiencia Hepática Crónica Agudizada/terapia , Intercambio Plasmático/métodos , Estudios Retrospectivos , Heparina/uso terapéutico , Calcio , Enfermedad Hepática en Estado Terminal/terapia , Índice de Severidad de la Enfermedad , Anticoagulantes/uso terapéutico
5.
J Mater Chem B ; 11(29): 6934-6942, 2023 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-37381888

RESUMEN

In areas of wound inflammation, excessive reactive oxygen species (ROS) may worsen the infection and lead to tissue damage, resulting in a vicious circle. Therefore, many hydrogels with sensitive ROS consumption capabilities and antibacterial properties have been widely developed and applied. These hydrogels usually achieve their ROS consumption capacity by introducing reactive active groups: however, these materials normally require complicated preparation procedures and have high potential toxicity. Inspired by these limitations, an integrated polyethylene glycol/alginate-based hydrogel (itg-PEGDA@SA) has been developed via a simple two-step process, where the inner PEGDA hydrogel (hdg-PEGDA) acts as a ROS scavenger and the outer sodium alginate hydrogel (SA) can be degraded to act as a recombinant human epidermal growth factor (rhEGF)-loaded platform to enhance the functionality of this composite hydrogel. Altogether, the itg-PEGDA@SA hydrogel showed significant ROS consumption and biocompatibility in vitro, and when applied for wound healing, the formation of uniform and ordered collagen fibers (stained using aniline blue) can be achieved. This hydrogel showed favorable attributes in ROS scavenging, and it can be a promising material for use in wound dressings and biomaterial fields.


Asunto(s)
Alginatos , Cicatrización de Heridas , Humanos , Especies Reactivas de Oxígeno/metabolismo , Materiales Biocompatibles/farmacología , Sulfanilamida , Hidrogeles/farmacología , Polietilenglicoles
6.
Angew Chem Int Ed Engl ; 61(11): e202116439, 2022 03 07.
Artículo en Inglés | MEDLINE | ID: mdl-34964238

RESUMEN

Non-invasive dynamic tracking of lysosomes and their interactions with other organelles is important for the study of lysosomal function and related diseases. However, many fluorescent dyes developed so far to target lysosomes cannot be used to monitor these processes due to the high concentrations required for imaging, long cell penetration times, and non-ideal photostability. In this regard, we synthesized three lysosomal targeting probes with large Stokes shifts, good stability, and high brightness. The Q-P-ARh dye, developed by us for the first time, can stain lysosomes at ultra-low concentrations (1.0 nM) without affecting the physiological functions of the lysosomes. More importantly, its excellent anti-interference ability and ultrafast lysosomal staining ability (within 1.0 min) clearly monitored the entire dynamic process of lipophagy. Ultimately, this method can greatly contribute to the study of autophagy pathways. This novel fluorescence platform shows great promise for the development of biological probes for application in pathological environments.


Asunto(s)
Autofagia , Fluorescencia , Colorantes Fluorescentes/química , Imagen Óptica , Colorantes Fluorescentes/síntesis química , Células Hep G2 , Humanos , Lisosomas/química
7.
Chem Commun (Camb) ; 57(12): 1510-1513, 2021 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33443242

RESUMEN

We present a ratiometric fluorescent probe for monitoring pH featuring superb photostability and chemostability. The down-regulation of the intracellular pH during autophagy in living cells induced by various stimuli, including several drugs and starvation, was quantified, which could provide instructive value to construct autophagy models to study the related pathological processes.


Asunto(s)
Autofagia/fisiología , Cumarinas/química , Colorantes Fluorescentes/química , Piridinas/química , Línea Celular Tumoral , Regulación hacia Abajo , Humanos , Concentración de Iones de Hidrógeno , Estructura Molecular
8.
Food Chem ; 341(Pt 2): 128254, 2021 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-33039741

RESUMEN

Different chemical states of nitrogen are present in many freshwater and marine ecosystems, and nitrite ions are one of the most toxic water-soluble nitrogen species. Developing an effective and convenient sensing method to constantly detect the concentration of nitrite has become a wide concern. Here, a novel near-infrared fluorescent probe (AAC) was designed and synthesized via the "covalent assembly" principle, showing excellent selectivity and high sensitivity for nitrite. A new nitrite-quantitative method was established with the help of AAC, and the detection limit of nitrite using the new method was as low as 6.7 nM. AAC was successfully applied for the quantitative detection of nitrite in real-world environmental and food samples (including river water and Chinese sauerkraut), and the detection results were essentially identical to the results obtained from the traditional Griess assay. Moreover, AAC was successfully applied for tracking nitrite in Escherichia coli by fluorescence imaging. Since nitrite can have devastating effects, the method established with AAC allowed us to "see" effectively about the water quality, food quality, etc.


Asunto(s)
Colorantes Fluorescentes/química , Nitritos/análisis , Espectroscopía Infrarroja Corta/métodos , Cumarinas/química , Escherichia coli/química , Agua Dulce/análisis , Límite de Detección
9.
ACS Appl Mater Interfaces ; 12(52): 57686-57694, 2020 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-33331759

RESUMEN

In recent years, hydrogels as an attractive class of intelligent soft materials have been applied in various advanced fields, including electronic materials, wearable devices, and wound dressing materials. However, it still remains a critical challenge to integrate information encryption transmission capability, antibacterial activity, high mechanical performance, adhesiveness, and self-healable ability into one material and achieve the synergistic characteristics through a simple method. In our study, a facile strategy of a plant-inspired hydrogel was proposed, which provides a novel initiator-free photo-cross-linked hydrogel system by simply mixing the coumarin derivative Pho-CA and the monomer in water, and then obtaining the hydrogel Gel-C-Am under the irradiation of UV light without adding any other cross-linking agents and initiators, and this process is very similar to the growth process of plants in nature. This novel hydrogel presents desirable mechanical properties (including twist, stretchability, and recoverability), which exhibits elongation of approximately 1600%. More interestingly, Gel-C-Am hydrogel displays reversible adhesiveness to various substrates (such as glass, paper, leaves, and rubber), and its adhesion properties can be regulated by water: the viscosity disappears when its surface becomes wet, and the viscosity will recover after the water evaporates. In addition, the developed hydrogel has certain self-healable ability. Two pieces of the Gel-C-Am hydrogel can combine together and reshape into one piece in water, and the fused hydrogel has uniform and interconnected pores under SEM. Based on the characteristic of Pho-CA whose fluorescence get recovery after UV irradiation, the hydrogel can be used in the field of encryption and decryption. Also, the resulting Gel-C-Am hydrogel shows an effective antibacterial activity and can potentially be addressed as antibacterial coatings. Taken together, the formation of the novel fluorescent hydrogel system is just like the growth of a plant in the presence of water and light, Pho-CA and the monomer will form a highly stretchable and recoverable self-healing hydrogel with water-controlled adhesiveness. The developed Gel-C-Am hydrogel shows favorable attributes and is suitable for applications in antibacterial polymeric coatings and information encryption transmission.


Asunto(s)
Biomimética , Seguridad Computacional , Colorantes Fluorescentes/química , Hidrogeles/química , Hidrogeles/farmacología , Plantas , Agua/química , Acrilamida/química , Adhesividad , Antibacterianos/química , Antibacterianos/farmacología , Cumarinas/química , Escherichia coli/efectos de los fármacos , Enlace de Hidrógeno , Propiedades de Superficie
10.
Chem Commun (Camb) ; 56(81): 12158-12161, 2020 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-32909575

RESUMEN

A highly reactive ylide tBuA was introduced, which could react rapidly with the 5-formyl and 4-amino groups of 5-formylcytosine (5fC) under mild conditions without any co-solvent or catalyst in a manner of Wittig olefination and intramolecular nucleophilic substitution to yield a cyclized fluorescent adduct, which meets the demands of both single-base resolution sequencing and fluorescence switch-on detection of 5fC in DNA.


Asunto(s)
Citosina/análogos & derivados , ADN/química , Colorantes Fluorescentes/química , Citosina/análisis , Teoría Funcional de la Densidad , Estructura Molecular , Agua/química
11.
Chem Commun (Camb) ; 56(50): 6870-6873, 2020 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-32432634

RESUMEN

A novel and efficient method to synthesize rigid bis-coumarins based on the dimerization of coumarinyl aldehydes was developed. This procedure is additive- and column-free, providing a facile and environment-friendly way to prepare fluorophores. The prepared novel fluorescent bis-coumarins exhibit favorable photophysical properties with good sensitivity and selectivity towards G-quadruplexes (G4s).

12.
BMC Gastroenterol ; 20(1): 106, 2020 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-32293297

RESUMEN

BACKGROUND: The purpose of this study is to investigate whether or not the complement system is systemically activated and to specify the clinical and prognostic implications of its components during hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF). METHODS: Blood samples were taken from twenty-seven patients diagnosed with HBV-ACLF, twenty-five patients diagnosed with chronic hepatitis B but without liver failure (CHB), and nine healthy volunteers (the control group). Plasma complement components were measured with Enzyme-linked immunosorbent assay. Correlative analysis were assessed between the levels of complement components and the liver failure related index. RESULTS: The concentrations of C3 was 6568 µg/ml in the HBV-ACLF group, 8916 µg/ml in the CHB group and 15,653 µg/ml in the control group, respectively (P <  0.05). The concentrations of C3a was 852 ng/ml in the HBV-ACLF group, 1008 ng/ml in the CHB group and 1755 ng/ml in the control group, respectively (P <  0.05). The concentrations of C1q was 50,509 ng/ml in the HBV-ACLF group, 114,640 ng/ml in the CHB group and 177,001 ng/ml in the control group, respectively (P <  0.05). The concentrations of C1q, C3, C3a, C4, C4a and sC5b-9 were significantly higher in the control group than those in the HBV-ACLF group (3.5, 2.4, 2.1, 1.4, 1.3 and 6.0 fold, respectively). However, there was no statistical significance of the differences in the plasma concentrations of mannose binding lectin and factor B between the HBV-ACLF group and control group. The levels of C3 and C3a were inversely correlated with MELDs or CLIF-C OFs (P <  0.05). CONCLUSIONS: Our analysis demonstrated that the activation of the classical pathway mediated by C1q may play an important role in the pathogenesis of HBV-ACLF. Furthermore, the plasma levels of C3 and C3a may be potential novel biomarkers in predicting the outcome of HBV-ACLF.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada/diagnóstico , Complemento C3/metabolismo , Hepatitis B Crónica/complicaciones , Insuficiencia Hepática Crónica Agudizada/sangre , Insuficiencia Hepática Crónica Agudizada/mortalidad , Insuficiencia Hepática Crónica Agudizada/virología , Adolescente , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Complemento C3a/metabolismo , Ensayo de Inmunoadsorción Enzimática , Femenino , Hepatitis B Crónica/sangre , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Índice de Severidad de la Enfermedad , Adulto Joven
13.
Nanoscale ; 12(3): 2002-2010, 2020 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-31912068

RESUMEN

A number of multimodal agents have been developed for tumour imaging and diagnosis, but most of them cannot be used to study the detailed physiological or pathological changes in living cells at the same time. Herein, a series of pH-responsive magnetic resonance and fluorescence imaging (MRI/FI) dual-modal "nanovehicles" are developed and tested. These new dual-modal materials allow for intercellular pH sensing, and those with units that are dually sensitive towards both acidic and basic environments have the ability for intracellular pH mapping and can be used to quantify pH at the cellular level. In addition, detailed pH changes in organelles (including lysosomes and mitochondria) can be investigated at the same time. On the other hand, with the tumour-targeting peptide (cRGD)-modified dual-modal nanovehicles, in vivo tumour MR and fluorescence imaging, which is suitable for cancer diagnosis, can be achieved. Moreover, it has been proved that these materials can pass through the blood brain barrier (BBB). By combining the above mentioned promising properties, these novel multifunctional "nanovehicles" may provide a new method for studying the role of pH during cancer diagnosis and treatment.


Asunto(s)
Sistemas de Liberación de Medicamentos , Oro , Imagen por Resonancia Magnética , Nanopartículas del Metal , Neoplasias Experimentales , Imagen Óptica , Animales , Femenino , Oro/química , Oro/farmacocinética , Oro/farmacología , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Células MCF-7 , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias Experimentales/diagnóstico por imagen , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Oligopéptidos/química , Oligopéptidos/farmacología , Ensayos Antitumor por Modelo de Xenoinjerto
14.
Anal Chem ; 92(4): 3262-3269, 2020 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-31957430

RESUMEN

A mitochondria targeting and immobilized fluorescent probe (Rd1) using triphenylphosphonium as the targeting group and methoxymaleimide as the fixed site is designed for the detection of ClO-. The methoxymaleimide fixed group can react with nucleophiles, such as the reactive thiol groups present in mitochondrial polypeptides and proteins, and form covalent bonds to immobilize the probe within mitochondria. The immobilization of Rd1 enhances its ability to withstand the risk of leakage from mitochondria. Methoxymaleimide shows better reactivity toward Cys than glutathione (GSH), which decreases the ineffective labeling of GSH when it covalently bonds with the reactive thiol residues of mitochondrial proteins; furthermore, it can resist hydrolysis during a long-term storage in water, compared with the classic benzyl chloride fixed unit. The imaging results indicate that Rd1 displays enhanced retention within the mitochondria of cells and tissues upon the decrease of mitochondrial membrane potential (MMP) caused by different stimulations. Furthermore, it possesses the ability to visualize exogenous and endogenous ClO- in living cells, tissues, and zebrafishes.


Asunto(s)
Colorantes Fluorescentes/química , Ácido Hipocloroso/química , Ácido Hipocloroso/metabolismo , Mitocondrias/metabolismo , Células A549 , Animales , Supervivencia Celular , Humanos , Ratones , Imagen Óptica , Células RAW 264.7 , Pez Cebra
15.
ACS Appl Bio Mater ; 3(1): 37-44, 2020 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-35019424

RESUMEN

Wound healing is a complex biological process, and the use of wound dressings is an effective adjunct to promote skin repair or tissue healing due to the limitations of skin self-healing. In this study, we constructed interpenetrating polymer network (IPN) hydrogels with HClO/ClO- indicative and biocompatible properties by combining sodium alginate (SA) and cross-linking RhB-AC. This hydrogel can also be used as a drug scaffold for controlled drug release. A significant fluorescence change was observed when hypochlorous acid was added to the hydrogel in vitro, which confirmed that the IPN hydrogel was able to indicate and consume a certain amount of hypochlorous acid. Subsequent cell culture and toxicity tests confirmed the good biocompatibility of the IPN hydrogel. When the hydrogel was used for wound healing in vivo, both the material itself and the hydrogel drug scaffold exhibited excellent wound healing effects. The present IPN hydrogels may be excellent candidates as hypochlorous acid consuming and biocompatible materials for wound dressing applications.

16.
Angew Chem Int Ed Engl ; 59(25): 9962-9966, 2020 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-31464051

RESUMEN

The abnormality of the plasma membrane (PM) is an important biomarker for cell status and many diseases. Hence, visualizing the PM, especially in complex systems, is an emerging field in the life sciences, especially in low-resource settings. Herein, we developed a water-soluble PM-specific probe utilizing electrostatic and hydrophobic interaction strategies with aggregation-induced emission as the signal output. The probe could image the PM with many advanced features (wash-free, ultrafast staining process, excellent PM specificity, and good biocompatibility), which were demonstrated by the PM imaging of neurons. The probe allowed for the first time the imaging of erythrocytes in the complex brain environment through a fluorescence-based method. Moreover, the PM of the epidermal and partial view of the eyeball structure of live zebrafish are also revealed.


Asunto(s)
Membrana Celular/ultraestructura , Colorantes Fluorescentes/química , Animales , Materiales Biocompatibles , Epidermis/ultraestructura , Eritrocitos/ultraestructura , Ojo/ultraestructura , Humanos , Neuronas/ultraestructura , Imagen Óptica , Espectrometría de Fluorescencia , Pez Cebra
17.
Anal Chem ; 91(15): 9366-9370, 2019 08 06.
Artículo en Inglés | MEDLINE | ID: mdl-31321977

RESUMEN

In view of the important epigenetic functions of 5-formylcytosine (5fC), the development of quantitative detection methods for 5fC is a long-standing issue. In this regard, how to distinguish 5fC from 5-formyluracil to achieve higher accuracy is particularly difficult because the latter one is more reactive. Herein, we reported a phosphorus ylide, YC-CN, and introduced a triple domino reaction to fluorescently switch on 5fC with excellent selectivity, which also enable us to quantify 5fC mutations induced by γ-irradiation. This Wittig-initiated covalent labeling strategy provide a novel strategy for qualitative and quantitative detection of 5fC.


Asunto(s)
Citosina/análogos & derivados , Citosina/análisis , Epigenómica , Fluorescencia , Rayos gamma/efectos adversos , Mutación/efectos de la radiación , Uracilo/análogos & derivados , Uracilo/análisis
18.
J Dig Dis ; 20(1): 38-44, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30515980

RESUMEN

OBJECTIVE: To investigate retrospectively the efficacy of steroids in patients with acute-on-chronic liver failure (ACLF) precipitated by hepatitis B. METHODS: Patients with ACLF precipitated by hepatitis B were included and categorized according to treatment modalities (steroid vs. control). Survival and clinical characteristics, including patients' age, baseline ACLF grade, the model for end-stage liver disease (MELD) score, and occurrence of infection were compared between the two groups. Survival analyses of subgroups classified by their age, ACLF grade and MELD score were performed. Cox regression analyses were conducted to identify factors associated with 60-day cumulative and transplant-free mortality. RESULTS: From 2007 to 2016, 293 patients with hepatitis B-precipitated ACLF were recruited, among whom 162 received at least five consecutive doses of corticosteroids. By day 60 transplant-free survival was 62.6% in the control group compared with 53.7% in the steroid group (P = 0.126). Steroid treatment failed to show a survival benefit in the survival analysis among the subgroup. Within 60 days, pulmonary and overall infections occurred with higher frequency in the steroid-treated group than in the controls (P = 0.003 and < 0.001, respectively). In the univariate analysis, age, baseline MELD score >20, CLIF consortium (CLIF-C) ACLF grade 2-3, pulmonary infection and overall infection were associated with 60-day mortality. In the multivariate analysis, older age, baseline MELD score >20 and CLIF-C ACLF grade 2-3 were independent risk factors of 60-day mortality. CONCLUSION: Steroid treatment did not improve transplant-free survival in patients with ACLF precipitated by hepatitis B.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada/tratamiento farmacológico , Insuficiencia Hepática Crónica Agudizada/virología , Glucocorticoides/uso terapéutico , Hepatitis B/complicaciones , Insuficiencia Hepática Crónica Agudizada/mortalidad , Adulto , Antivirales/uso terapéutico , China , Femenino , Hospitales Universitarios , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento
19.
Chem Commun (Camb) ; 54(97): 13722-13725, 2018 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-30452024

RESUMEN

The chemically selective detection of natural nucleobase modifications has been regarded as the key step in understanding their important roles in epigenetics. Herein, for the first time, we introduce a Wittig reaction into the design of reaction-based fluorescent probes for ratiometrically detecting 5fU, selectively labelling 5fU-modified DNA and imaging intracellular 5fU produced by γ-irradiation.


Asunto(s)
Células/química , Colorantes Fluorescentes/química , Imagen Óptica , Uracilo/análogos & derivados , Células/metabolismo , Colorantes Fluorescentes/síntesis química , Células HeLa , Humanos , Estructura Molecular , Espectrometría de Fluorescencia , Uracilo/análisis
20.
Medicine (Baltimore) ; 96(17): e6802, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28445322

RESUMEN

Acute-on-chronic liver failure (ACLF) in chronic hepatitis B (CHB) patients has a high short-term mortality. Identification of effective models to predict the short-term mortality may enable early intervention and improve patients' prognosis. We aim to assess the performance of the CLIF Consortium Organ Failure score (CLIF-C OFs), CLIF sequential organ failure assessment score (CLIF-SOFAs), CLIF Consortium ACLF score (CLIF-C ACLFs), ACLF grade, and model for end-stage liver disease score (MELDs) in predicting the short-term mortality in CHB patients with ACLF.Among the 155 consecutive adult patients with liver failure as a discharge diagnosis were screened, and all the patients were treated at the Department of Infectious Diseases, Huashan Hospital, Fudan University (Shanghai, China) from January 2010 to February 2016. The diagnosis of ACLF was based on the criteria formalized by the ACLF consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL). Diagnostic accuracy for predicting short-term (28-day) mortality was calculated for CLIF-C OFs, CLIF-SOFAs, CLIF-C ACLFs, ACLF grade, and MELDs in all patients.One hundred fifty-five consecutive adult liver failure patients were screened and 85 patients including 73 males and 12 females were enrolled. Overall, the 28-day transplant-free mortality was 32% in all patients, and 100% in those with severe early course (ACLF-3). The area under the receiver operating characteristic curve (AUROC) of CLIF-C OFs (AUROC: 0.906, P = .0306, compared with MELDs) was higher than those of CLIF-SOFAs (AUROC: 0.876), CLIF-C ACLFs (AUROC: 0.858), ACLF grade (AUROC: 0.857), and MELDs (AUROC: 0.838) for predicting short-term mortality. The cut-point for baseline CLIF-C OFs in predicting death was 8.5, with 67% sensitivity, 90% specificity, and AUROC of 0.906 (95% CI: 0.8450-0.9679).The results indicate that short-term mortality is high in patients with ACLF and CLIF Consortium Organ Failure score is superior to MELD, CLIF SOFA, and CLIF-C ACLF in predicting its short-term mortality.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada/diagnóstico , Insuficiencia Hepática Crónica Agudizada/mortalidad , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/mortalidad , Gravedad del Paciente , Insuficiencia Hepática Crónica Agudizada/complicaciones , Adolescente , Adulto , Anciano , Área Bajo la Curva , Femenino , Hepatitis B Crónica/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Factores de Tiempo , Adulto Joven
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