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1.
Chem Soc Rev ; 53(10): 5149-5189, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38566609

RESUMEN

The electrochemical reduction of CO2 into value-added chemicals has been explored as a promising solution to realize carbon neutrality and inhibit global warming. This involves utilizing the electrochemical CO2 reduction reaction (CO2RR) to produce a variety of single-carbon (C1) and multi-carbon (C2+) products. Additionally, the electrolyte solution in the CO2RR system can be enriched with nitrogen sources (such as NO3-, NO2-, N2, or NO) to enable the synthesis of organonitrogen compounds via C-N coupling reactions. However, the electrochemical conversion of CO2 into valuable chemicals still faces challenges in terms of low product yield, poor faradaic efficiency (FE), and unclear understanding of the reaction mechanism. This review summarizes the promising strategies aimed at achieving selective production of diverse carbon-containing products, including CO, formate, hydrocarbons, alcohols, and organonitrogen compounds. These approaches involve the rational design of electrocatalysts and the construction of coupled electrocatalytic reaction systems. Moreover, this review presents the underlying reaction mechanisms, identifies the existing challenges, and highlights the prospects of the electrosynthesis processes. The aim is to offer valuable insights and guidance for future research on the electrocatalytic conversion of CO2 into carbon-containing products of enhanced value-added potential.

2.
J Proteome Res ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38980715

RESUMEN

Hepatocellular carcinoma (HCC) mortality rates continue to increase faster than those of other cancer types due to high heterogeneity, which limits diagnosis and treatment. Pathological and molecular subtyping have identified that HCC tumors with poor outcomes are characterized by intratumoral collagenous accumulation. However, the translational and post-translational regulation of tumor collagen, which is critical to the outcome, remains largely unknown. Here, we investigate the spatial extracellular proteome to understand the differences associated with HCC tumors defined by Hoshida transcriptomic subtypes of poor outcome (Subtype 1; S1; n = 12) and better outcome (Subtype 3; S3; n = 24) that show differential stroma-regulated pathways. Collagen-targeted mass spectrometry imaging (MSI) with the same-tissue reference libraries, built from untargeted and targeted LC-MS/MS was used to spatially define the extracellular microenvironment from clinically-characterized, formalin-fixed, paraffin-embedded tissue sections. Collagen α-1(I) chain domains for discoidin-domain receptor and integrin binding showed distinctive spatial distribution within the tumor microenvironment. Hydroxylated proline (HYP)-containing peptides from the triple helical regions of fibrillar collagens distinguished S1 from S3 tumors. Exploratory machine learning on multiple peptides extracted from the tumor regions could distinguish S1 and S3 tumors (with an area under the receiver operating curve of ≥0.98; 95% confidence intervals between 0.976 and 1.00; and accuracies above 94%). An overall finding was that the extracellular microenvironment has a high potential to predict clinically relevant outcomes in HCC.

3.
Langmuir ; 40(12): 6550-6561, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38483322

RESUMEN

With environmental pollution becoming more serious, developing efficient treatment technologies for all kinds of organic wastewater has become the focus of current research. In this work, the coaxial electrospinning technology was used to one-step fabricate a porous and underwater superoleophobic polyacrylonitrile nanofibrous membrane with an Fe-based metal-organic framework (MIL-100(Fe)). Benefiting from the synergistic effect of two jets, the nanofibers are smaller and denser, which prompt the exposure of more nanomaterial additives (MIL-100(Fe)). The BET surface area increased to 202.888 m2/g, and the membranes demonstrated outstanding underwater superoleophobicity. Moreover, compared with traditional blended matrix membranes by the single-axis method, separation of the modifier and membrane matrix material by coaxial methods also maintained excellent mechanical properties, which enhanced Young's modulus 3.4 times (∼1.34 MPa). As a result, facing soluble dyes, the porous C-PAN/MIL-100(Fe) membrane can demonstrate outstanding and fast adsorptive property (the Qm of MB and CR reached 44.71 and 88.74 mg g-1, respectively). For oily emulsion, the hydrophilic and oleophobic nanofibrous reticular surface provided excellent separation performance (flux: 1124.0-1549.3 L m-2 h-1, R > 98%). Moreover, the porous and underwater superoleophobic C-PAN/MIL-100(Fe)-0.5 membrane can synchronously purify the dye/oil mixture emulsions by one-step filtration. Based on the above performance, we believe that the modified nanofibrous membrane prepared by one-step coaxial electrospinning technology can promote more studies of the development of membrane preparation technology in the field of oily wastewater treatment.

4.
Avian Pathol ; : 1-10, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38922304

RESUMEN

RESEARCH HIGHLIGHTS: First confirmation of AOAV-16 in domestic and wild birds in China.AOAV-16 are low virulent viruses for chickens.Co-circulation/co-infection of AOAV-16 and H9N2 subtype AIV enhanced pathogenicity.Different intergenic sequences and recombination events exist within AOAV-16.

5.
Perfusion ; : 2676591241242641, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38553982

RESUMEN

BACKGROUND: The lysine analog tranexamic acid (TXA) is used as a blood protective drug in cardiac surgery, but efficacy and safety outcomes in patients treated with extracorporeal membrane oxygenation (ECMO) after surgery remain poorly understood. METHODS: From January 1, 2017 to December 31, 2022, we retrospectively analyzed patients assisted by ECMO after cardiac surgery and divided them into TXA and control groups depending on whether TXA was used or not. The primary study outcome was red blood cell (RBC) transfusion during ECMO. RESULTS: In total, 321 patients treated with ECMO after cardiac surgery were assessed; 185 patients were eligible for inclusion into to the TXA-intervention group and 136 into to the control group. RBC transfusion during ECMO was 8.0 IU (4.0 IU-14.0 IU) in the TXA group versus 10.0 IU (6.0 IU-16.0 IU) in the control group (p = .034). Median total chest drainage volume after surgery was 1460.0 mL (650.0-2910.0 mL) and 1680.0 mL (900.0-3340.0 mL) in TXA and control groups, respectively (p = .021). Postoperative serum D-dimer levels were significantly lower in the TXA group when compared with the control group; 1.125 µg/mL (0.515-2.176 µg/mL) versus 3.000 µg/mL (1.269-5.862 µg/mL), p < .001. Serious adverse events, including vascular occlusive events, did not differ meaningfully between groups. CONCLUSIONS: In patients treated with ECMO after cardiac surgery, TXA infusion modestly but significantly reduced RBC transfusions and chest tube output when compared with the control group.

6.
J Transl Med ; 21(1): 900, 2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-38082327

RESUMEN

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) accounts for about 15% of primary liver cancer, and the incidence rate has been rising in recent years. Surgical resection is the best treatment for ICC, but the 5-year survival rate is less than 30%. ICC signature genes are crucial for the early diagnosis of ICC, so it is especially important to find its signature genes and therapeutic drug. Here, we studied that bufalin targeting CAMKK2 promotes mitochondrial dysfunction and inhibits the occurrence and metastasis of intrahepatic cholangiocarcinoma through Wnt/ß-catenin signal pathway. METHODS: IC50 of bufalin in ICC cells was determined by CCK8 and invasive and migratory abilities were verified by wound healing, cell cloning, transwell and Western blot. IF and IHC verified the expression of CAMKK2 between ICC patients and normal subjects. BLI and pull-down demonstrated the binding ability of bufalin and CAMKK2. Bioinformatics predicted whether CAMKK2 was related to the Wnt/ß-catenin pathway. SKL2001, an activator of ß-catenin, verified whether bufalin acted through this pathway. In vitro and in vivo experiments verified whether overexpression of CAMKK2 affects the proliferative and migratory effects of ICC. Transmission electron microscopy verified mitochondrial integrity. Associated Ca2+ levels verified the biological effects of ANXA2 on ICC. RESULTS: It was found that bufalin inhibited the proliferation and migration of ICC, and CAMKK2 was highly expressed in ICC, and its high expression was positively correlated with poor prognosis.CAMKK2 is a direct target of bufalin, and is associated with the Wnt/ß-catenin signaling pathway, which was dose-dependently decreased after bufalin treatment. In vitro and in vivo experiments verified that CAMKK2 overexpression promoted ICC proliferation and migration, and bufalin reversed this effect. CAMKK2 was associated with Ca2+, and changes in Ca2+ content induced changes in the protein content of ANXA2, which was dose-dependently decreasing in cytoplasmic ANXA2 and dose-dependently increasing in mitochondrial ANXA2 after bufalin treatment. In CAMKK2 overexpressing cells, ANXA2 was knocked down, and we found that reversal of CAMKK2 overexpression-induced enhancement of ICC proliferation and migration after siANXA2. CONCLUSIONS: Our results suggest that bufalin targeting CAMKK2 promotes mitochondrial dysfunction and inhibits the proliferation and migration of intrahepatic cholangiocarcinoma through Wnt/ß-catenin signal pathway. Thus, bufalin, as a drug, may also be used for cancer therapy in ICC in the future.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Enfermedades Mitocondriales , Humanos , Vía de Señalización Wnt , beta Catenina/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/genética , Colangiocarcinoma/patología , Conductos Biliares Intrahepáticos/metabolismo , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/genética , Neoplasias de los Conductos Biliares/patología , Enfermedades Mitocondriales/genética , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/genética , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/metabolismo
7.
Crit Rev Food Sci Nutr ; : 1-36, 2022 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-36123805

RESUMEN

The consumption of fresh fruits and vegetables is restricted by the susceptibility of fresh produce to deterioration caused by postharvest physiological and metabolic activities. Developing efficient preservation strategies is thus among the most important scientific issues to be urgently addressed in the field of food science. The incorporation of active agents into a polymer matrix to prepare biodegradable active packaging is being increasingly explored to mitigate the postharvest spoilage of fruits and vegetables during storage. This paper reviews the composition of biodegradable polymers and the methods used to prepare biodegradable active packaging. In addition, the interactions between bioactive ingredients and biodegradable polymers that can lead to plasticizing or cross-linking effects are summarized. Furthermore, the applications of biodegradable active (i.e., antibacterial, antioxidant, ethylene removing, barrier, and modified atmosphere) packaging in the preservation of fruits and vegetables are illustrated. These films may increase sensory acceptability, improve quality, and prolong the shelf life of postharvest products. Finally, the challenges and trends of biodegradable active packaging in the preservation of fruits and vegetables are discussed. This review aims to provide new ideas and insights for developing novel biodegradable active packaging materials and their practical application in the preservation of postharvest fruits and vegetables.

8.
J Am Chem Soc ; 143(40): 16512-16518, 2021 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-34601870

RESUMEN

Heterojunction nanostructures usually exhibit enhanced properties in compariosn with their building blocks and are promising catalyst candidates due to their combined surface and unique interface. Here, for the first time we realized the oriented growth of ultrasmall metal nanoparticles (NPs) on metal-organic framework nanosheets (MOF NSs) by precisely regulating the reduction kinetics of metal ions with solvents. In particular, a rapid reduction of metal ions leads to the random distribution of metal NPs on the surface of MOF NSs, while a slow reduction of metal ions results in the oriented growth of NPs on the edge of MOF NSs. Impressively, the strong synergy between Pt NPs and MOF NSs significantly enhances the hydrogen evolution reaction (HER) performance, and the optimal catalyst displays HER activities superior to those of a composite with a random growth of Pt NPs and commercial Pt/C under both acidic and alkaline conditions. Moreover, the versatility of such oriented growth has been extended to other metal NPs, such as Pd, Ag, and Au. We believe this work will promote research interest in material design for many potential applications.

9.
Angew Chem Int Ed Engl ; 60(20): 11190-11195, 2021 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-33694245

RESUMEN

Two-dimensional (2D) metal-organic framework nanosheets (MOF NSs) play a vital role in catalysis, but the most preparation is ultrasonication or solvothermal. Herein, a liquid-liquid interfacial synthesis method has been developed for the efficient fabrication of a series of 2D Ni MOF NSs. The active sites could be modulated by readily tuning the ratios of metal precursors and organic linkers (RM/L ). The Ni MOF NSs display highly RM/L dependent activities towards 2e oxygen reduction reaction (ORR) to hydrogen peroxide (H2 O2 ), where the Ni MOF NSs with the RM/L of 6 exhibit the optimal near-zero overpotential, ca. 98 % H2 O2 selectivity and production rate of ca. 80 mmol gcat -1 h-1 in 0.1 M KOH. As evidenced by X-ray absorption fine structure spectroscopy, the coordination environment of active sites changed from saturation to unsaturation, and the partially unsaturated metal atoms are crucial to create optimal sites for enhancing the electrocatalysis.

10.
Analyst ; 145(17): 5808-5815, 2020 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-32672281

RESUMEN

In this work, a novel ratiometric fluorescent platform for α-glucosidase (α-glu) and its inhibitor was constructed based on N-doped carbon dots (N-CDs). The α-glucosidase present can catalyze the release of hydroquinone (HQ) from α-arbutin. Then, the generated HQ can be oxidized and copolymerized with polyethyleneimine (PEI) to form a yellowish green fluorescence copolymer (PHQ-PEI) with intense fluorescence emission at 510 nm. When the PHQ-PEI was formed, blue fluorescence of N-CDs at 425 nm was decreased, whereas the fluorescence of PHQ-PEI at 510 nm increased sharply as a result of the fluorescence resonance energy transfer (FRET) effect between N-CDs and PHQ-PEI. However, in the presence of acarbose, the activity of α-glucosidase is inhibited, and α-arbutin cannot be hydrolyzed to hydroquinone, leading to the fluorescence recovery of N-CDs at 425 nm and the fluorescence decrease of PHQ-PEI at 510 nm. The linear range from 0.2 to 1.6 mU mL-1 and 25-150 µmol L-1 was obtained for α-glucosidase and acarbose detection, respectively, and the detection limit (LOD) for α-glucosidase and acarbose was as low as 0.082 mU mL-1 and 14.5 µmol L-1. Thus, a ratiometric fluorescent sensor with good sensitivity and high specificity was established for α-glucosidase assay and satisfactory results were acquired in real sample determination.


Asunto(s)
Técnicas Biosensibles , Puntos Cuánticos , Acarbosa , Carbono , alfa-Glucosidasas
11.
Analyst ; 145(3): 1001-1007, 2020 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-31830153

RESUMEN

Herein, papain-protected bimetallic gold/silver nanoclusters (Au/Ag NCs) were successfully synthesized and applied for the detection of ascorbate oxidase (AAO). The doping of papain-protected Au nanoclusters with Ag enhanced the fluorescence intensity with an intense red fluorescence peak at 617 nm, and the red-emitting Au/Ag nanoclusters were further used to monitor the AAO activity. The fluorescence of Au/Ag NCs could be quenched by hydrogen peroxide (H2O2) due to the generation of hydroxyl radicals (˙OH) from the reaction of Ag/Au nanoclusters and H2O2. However, the addition of ascorbic acid (AA) effectively reacted with the free radicals and caused the fluorescence recovery of the Au/Ag NCs. Furthermore, AAO could catalyze the oxidation of AA to form dehydro-ascorbate (DHA). As a result, there was not enough AA to consume the hydroxyl radicals, which resulted in a decrease in the fluorescence of the papain-capped Au/Ag NCs. Therefore, the AAO activity can be monitored by measuring the fluorescence intensity of the red-emitting Au/Ag NCs. Moreover, the developed method for AAO detection displayed a good linear relationship from 5 to 80 mU mL-1 and the detection limit was 1.72 mU mL-1. Thus, a simple and selective method for the determination of the AAO activity was constructed and satisfactory results were obtained in real sample detection.


Asunto(s)
Ascorbato Oxidasa/metabolismo , Oro/química , Nanopartículas del Metal/química , Plata/química , Espectrometría de Fluorescencia/métodos , Ascorbato Oxidasa/sangre , Ácido Ascórbico/análisis , Ácido Ascórbico/química , Ácido Ascórbico/metabolismo , Biocatálisis , Humanos , Peróxido de Hidrógeno/química , Radical Hidroxilo/química , Radical Hidroxilo/metabolismo , Límite de Detección , Oxidación-Reducción , Papaína/química , Papaína/metabolismo , Reproducibilidad de los Resultados
12.
Angew Chem Int Ed Engl ; 59(34): 14373-14377, 2020 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-32453471

RESUMEN

Herein, we developed a partially controlled pyrolysis strategy to create evenly distributed NiO nanoparticles within NiFe-MOF nanosheets (MOF NSs) for electrochemical synthesis of H2 O2 by a two-electron oxygen reduction reaction (ORR). The elemental Ni can be partially transformed to NiO and uniformly distributed on the surface of the MOF NSs, which is crucial for the formation of the particular structure. The optimized MOF NSs-300 exhibits the highest activity for ORR with near-zero overpotential and excellent H2 O2 selectivity (ca. 99 %) in 0.1 m KOH solution. A high-yield H2 O2 production rate of 6.5 mol gcat -1 h-1 has also been achieved by MOF NSs-300 in 0.1 m KOH and at 0.6 V (vs. RHE). In contrast to completely pyrolyzed products, the enhanced catalytic activities of partially pyrolyzed MOF NSs-300 originates mainly from the retained MOF structure and the newly generated NiO nanoparticles, forming the coordinatively unsaturated Ni atoms and tuning the performance towards electrochemical H2 O2 synthesis.

13.
Anal Chem ; 91(13): 8429-8435, 2019 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-31177770

RESUMEN

A new platform for N-glycoprotein analysis from serum that combines matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) workflows with antibody slide arrays is described. Antibody panel based (APB) N-glycan imaging allows for the specific capture of N-glycoproteins by antibodies on glass slides and N-glycan analysis in a protein-specific and multiplexed manner. Development of this technique has focused on characterizing two abundant and well-studied human serum glycoproteins, alpha-1-antitrypsin and immunoglobulin G. Using purified standard solutions and 1 µL samples of human serum, both glycoproteins can be immunocaptured and followed by enzymatic release of N-glycans. N-Glycans are detected with a MALDI FT-ICR mass spectrometer in a concentration-dependent manner while maintaining specificity of capture. Importantly, the N-glycans detected via slide-based antibody capture were identical to that of direct analysis of the spotted standards. As a proof of concept, this workflow was applied to patient serum samples from individuals with liver cirrhosis to accurately detect a characteristic increase in an IgG N-glycan. This novel approach to protein-specific N-glycan analysis from an antibody panel can be further expanded to include any glycoprotein for which a validated antibody exists. Additionally, this platform can be adapted for analysis of any biofluid or biological sample that can be analyzed by antibody arrays.


Asunto(s)
Biomarcadores/metabolismo , Glicómica/métodos , Glicoproteínas/metabolismo , Cirrosis Hepática/diagnóstico , Imagen Óptica/métodos , Polisacáridos/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Estudios de Casos y Controles , Glicoproteínas/química , Glicosilación , Humanos , Cirrosis Hepática/metabolismo , Polisacáridos/química
14.
Sensors (Basel) ; 19(20)2019 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-31640136

RESUMEN

This paper derives an improved multistage in-motion attitude determination alignment (IMADA) for strapdown inertial navigation system, which integrates the traditional IMADA and the designed dual velocity-modeling IMADA, as well as the multiple repeated alignment process, to address the principled model errors and the calculation errors of traditional V b -aided IMADA. With the proposed algorithm, not only the designed drawbacks of traditional V b -based IMADA can be solved, but also the degradation phenomenon of high-level alignment for multistage IMADA would be largely less. Moreover, the degradation of the alignment accuracy with the vehicle velocity is also removed. Finally, the 30 groups of car-mounted experiments and the Monte Carlo simulation experiments with the navigation-grade SINS are carried out to demonstrate the validity of the proposed algorithm. The results show that the number of the heading degradation of the second-level alignment is reduced to 10 as compared the traditional number 20. Moreover, the alignment accuracy of heading is improved by 23%. Even with the different speeds of 20 m/s, 60 m/s, 80 m/s, the heading alignment accuracies are 1.3063°, 1.3102°, 1.3564° and are still almost the same.

15.
Int J Mol Sci ; 20(10)2019 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-31126011

RESUMEN

(1) Glycoproteins account for ~80% of proteins located at the cell surface and in the extracellular matrix. A growing body of evidence indicates that α-L-fucose protein modifications contribute to breast cancer progression and metastatic disease. (2) Using a combination of techniques, including matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) based in cell and on tissue imaging and glycan sequencing using exoglycosidase analysis coupled to hydrophilic interaction ultra-high performance liquid chromatography (HILIC UPLC), we establish that a core-fucosylated tetra-antennary glycan containing a single N-acetyllactosamine (F(6)A4G4Lac1) is associated with poor clinical outcomes in breast cancer, including lymph node metastasis, recurrent disease, and reduced survival. (3) This study is the first to identify a single N-glycan, F(6)A4G4Lac1, as having a correlation with poor clinical outcomes in breast cancer.


Asunto(s)
Amino Azúcares/análisis , Neoplasias de la Mama/patología , Fucosa/análisis , Polisacáridos/análisis , Animales , Línea Celular Tumoral , Cromatografía Líquida de Alta Presión , Femenino , Glicoproteínas/química , Glicosilación , Humanos , Ganglios Linfáticos/patología , Ratones Endogámicos BALB C , Metástasis de la Neoplasia/patología , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Análisis de Supervivencia
16.
J Proteome Res ; 17(10): 3454-3462, 2018 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-30110170

RESUMEN

Hepatocellular carcinoma (HCC) remains as the fifth most common cancer in the world and accounts for more than 700,000 deaths annually. Changes in serum glycosylation have long been associated with this cancer but the source of that material is unknown and direct glycan analysis of HCC tissues has been limited. Our laboratory previously developed a method of in situ tissue based N-linked glycan imaging that bypasses the need for microdissection and solubilization of tissue prior to analysis. We used this methodology in the analysis of 138 HCC tissue samples and compared the N-linked glycans in cancer tissue with either adjacent untransformed or tissue from patients with liver cirrhosis but no cancer. Ten glycans were found significantly elevated in HCC tissues as compared to cirrhotic or adjacent tissue. These glycans fell into two major classes, those with increased levels of fucosylation and those with increased levels of branching with or without any fucose modifications. In addition, increased levels of fucosylated glycoforms were associated with a reduction in survival time. This work supports the hypothesis that the increased levels of fucosylated N-linked glycans in HCC serum are produced directly from the cancer tissue.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Cirrosis Hepática/metabolismo , Neoplasias Hepáticas/metabolismo , Hígado/metabolismo , Polisacáridos/metabolismo , Adulto , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/patología , Femenino , Fucosa/metabolismo , Glicosilación , Histocitoquímica/métodos , Humanos , Estimación de Kaplan-Meier , Hígado/patología , Cirrosis Hepática/sangre , Cirrosis Hepática/patología , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Polisacáridos/química , Análisis de Matrices Tisulares/métodos
17.
Pharmacol Res ; 131: 102-111, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29530599

RESUMEN

Renal fibrosis is recognized as the common route of all chronic kidney disease (CKD) progressing to end-stage renal disease (ESRD). Additionally, accumulating evidence suggests that epithelial-mesenchymal transition (EMT) plays a significant role in the process of renal fibrogenesis. Liraglutide is a long-acting glucagon-like peptide-1 (GLP-1) analog that has been widely used to treat type 2 diabetes. Recent studies have demonstrated that the GLP-1 analogs could also exert protective effects in cardiac fibrosis models. However, the effects of liraglutide on the progression of CKD remain largely unknown. In the present study, we investigated the effects of liraglutide on the progression to renal fibrosis induced by unilateral ureteral obstruction (UUO) and EMT of rat renal tubular epithelial cells (NRK-52E) induced with recombinant transforming growth factor-beta 1 (TGF-ß1). The results indicated that UUO increased collagen deposition and the mRNA expression of fibronectin (FN) and collagen type I alpha 1 (Col1α1) in the obstructed kidney tissues. The effects were blunted in liraglutide-treated UUO mice compared with control mice. The upregulation of Snail1 and alpha smooth muscle actin (α-SMA), and downregulation of E-cadherin revealed that EMT occurred in the UUO kidneys, and these effects were ameliorated following liraglutide treatment. Additionally, liraglutide treatment decreased the expression of TGF-ß1 and its receptor (TGF-ß1R) and inhibited the activation of its downstream signaling molecules (pSmad3 and pERK1/2). The in vitro results showed that the EMT and extracellular matrix (ECM) secretion of NRK-52E cells were induced by TGF-ß1. In addition, the Smad3 and ERK1/2 signaling pathways were highly activated in cells cultured with TGF-ß1. All these effects were attenuated by liraglutide treatment. However, the protective effects of liraglutide were abolished by co-incubation of the GLP-1 receptor (GLP-1R) antagonist exendin-3 (9-39). These results suggest that liraglutide attenuates the EMT and ECM secretion of NRK-52E cells induced by TGF-ß1 and EMT and renal fibrosis induced by UUO. The potential mechanism involves liraglutide binding to and activating GLP-1R, which prevents EMT by inhibiting the activation of TGF-ß1/Smad3 and ERK1/2 signaling pathways, thereby decreasing the ECM secretion and deposition. Therefore, liraglutide is a promising therapeutic agent that may halt the progression of renal fibrosis.


Asunto(s)
Hipoglucemiantes/uso terapéutico , Riñón/efectos de los fármacos , Riñón/patología , Liraglutida/uso terapéutico , Obstrucción Ureteral/tratamiento farmacológico , Animales , Línea Celular , Colágeno/análisis , Colágeno/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Fibrosis , Péptido 1 Similar al Glucagón/análogos & derivados , Péptido 1 Similar al Glucagón/uso terapéutico , Riñón/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratas , Transducción de Señal/efectos de los fármacos , Obstrucción Ureteral/complicaciones , Obstrucción Ureteral/metabolismo , Obstrucción Ureteral/patología
18.
BMC Nephrol ; 19(1): 90, 2018 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-29669532

RESUMEN

BACKGROUND: Pulmonary lymphangioleimyomatosis (PLAM) is a rare disease involving lung. PLAM primarily affects young women, a characteristic it shares with systemic lupus erythematosus (SLE). Estrogen has long been assumed to play an important role both in PLAM and SLE. We report a menopausal woman, who was found to have PLAM 1 year after she was diagnosed with SLE. Her chest radiograph was normal in the early phase of SLE. CASE PRESENTATION: A 52-year-old Chinese woman was referred to our hospital in August 2014 because of swelling in both legs. She also reported a malar rash and intermittent generalized arthralgia. Laboratory examination showed leukopenia. Her serum albumin level was 23 g/L; 24-h urinary protein excretion was 5.3 g. She tested positive for anti-Smith (Sm) antibody and anti-SS-A antibody. Renal biopsy indicated Class V + IV(G)-A lupus nephritis (LN). The condition of SLE and LN improved on a regime of tapering prednisolone and intermittent intravenous cyclophosphamide therapy until 1 year later when she developed exertional dyspnea accompanied with frequent cough. Thoracic computed tomography revealed numerous well-defined cysts and the diagnosis of PLAM was confirmed by lung biopsy. In the follow-up period, the patient continued to be on prednisolone and mycophenolate mofetil for the treatment of SLE, but only agreed to receive symptomatic treatment for PLAM. One year after the diagnosis of PLAM, during which time the SLE was stable, she died of respiratory failure and cor pulmonale. CONCLUSION: We report a patient with coexisting SLE and PLAM, who was treated with immunosuppressive therapy. SLE was stable but PLAM was not improved. Although the coexistence of SLE and PLAM might be a coincidence, the occurrence of these two diseases in a menopausal woman may warrant further mechanistic exploration.


Asunto(s)
Leiomiomatosis/complicaciones , Neoplasias Pulmonares/complicaciones , Nefritis Lúpica/complicaciones , Linfangioma/complicaciones , Menopausia , Antibacterianos/uso terapéutico , Ciclofosfamida/uso terapéutico , Quimioterapia Combinada , Resultado Fatal , Femenino , Humanos , Inmunosupresores/uso terapéutico , Leiomiomatosis/terapia , Neoplasias Pulmonares/terapia , Nefritis Lúpica/tratamiento farmacológico , Linfangioma/terapia , Metilprednisolona/uso terapéutico , Persona de Mediana Edad , Ácido Micofenólico/uso terapéutico , Neumonía Bacteriana/complicaciones , Neumonía Bacteriana/tratamiento farmacológico , Prednisolona/uso terapéutico
20.
Proteomics ; 16(24): 3126-3136, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27650323

RESUMEN

The Aleuria aurantia lectin (AAL) derived from orange peel fungus contains five fucose-binding sites that recognizes fucose bound in α-1,2, α-1,3, α-1,4, and α-1,6 linkages to N-acetylglucosamine and galactose. Recently, we have created several recombinant AAL (rAAL) proteins that had altered binding affinity to fucose linkages. In this report, we further characterize the binding specificity of one of the mutated lectins, N224Q lectin. This lectin was characterized by lectin Western blotting, surface plasmon resonance, and glycan microarray and shown to have increased binding to fucosylated glycan. Subsequently, we used this lectin to identify secreted fucosylated glycoproteins from a fetal hepatic cell line. Proteomic analysis revealed several glycoproteins secreted by the fetal cell line that were bound by N224Q lectin. These findings were confirmed by subsequent proteomic analysis of human serum from control patients or patients with hepatocellular carcinoma. These represent candidate oncofetal markers for liver cancer.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Fucosa/metabolismo , Glicoproteínas/metabolismo , Lectinas/metabolismo , Neoplasias Hepáticas/metabolismo , Polisacáridos/metabolismo , Ascomicetos/química , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/diagnóstico , Línea Celular , Células Cultivadas , Fucosa/análisis , Glicoproteínas/análisis , Hepatocitos/metabolismo , Hepatocitos/patología , Humanos , Lectinas/química , Hígado/metabolismo , Hígado/patología , Neoplasias Hepáticas/diagnóstico , Polisacáridos/química , Unión Proteica , Proteómica , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo
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