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1.
J Am Chem Soc ; 146(6): 3651-3659, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38301131

RESUMEN

The search for long molecular wires that can transport charge with maximum efficiency over many nanometers has driven molecular electronics since its inception. Single-molecule conductance normally decays with length and is typically far below the theoretical limit of G0 (77.5 µS). Here, we measure the conductances of a family of edge-fused porphyrin ribbons (lengths 1-7 nm) that display remarkable behavior. The low-bias conductance is high across the whole series. Charging the molecules in situ results in a dramatic realignment of the frontier orbitals, increasing the conductance to 1 G0 (corresponding to a current of 20 µA). This behavior is most pronounced in the longer molecules due to their smaller HOMO-LUMO gaps. The conductance-voltage traces frequently exhibit peaks at zero bias, showing that a molecular energy level is in resonance with the Fermi level. This work lays the foundations for long, perfectly transmissive, molecular wires with technological potential.

2.
Pediatr Transplant ; 28(3): e14737, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38602290

RESUMEN

BACKGROUND: Venous complications after pediatric liver transplantation seriously affect the survival rate of patients and grafts. At present, the diagnostic indicators have not been unified. Venous complications may cause portal hypertension, which may lead to splenomegaly and splenic vein dilatation. Therefore, the changes in spleen may be closely related to the venous complications. The purpose of this study was to explore the relationship between ultrasonic splenic parameters and venous complications and to study whether these splenic parameters can be used for the diagnosis of venous complications. METHODS: We retrospectively included pediatric patients who underwent liver transplantation and collected ultrasonic spleen parameters before, and then 1-3 days, 1-3 weeks, 1-3 months, and 4-12 months after liver transplantation. We observed whether there were portal vein or hepatic vein complications within 1 year after liver transplantation. RESULTS: Among 109 pediatric patients after liver transplantation included in our study, 11 of them suffered from portal vein complications and nine hepatic vein complications. Spleen transverse diameter, spleen longitudinal diameter, spleen portal vein diameter, spleen index, spleen transverse diameter ratio, spleen longitudinal diameter ratio, and spleen index ratio were independent risk factors of venous complications. The accuracy of spleen transverse diameter (AUROC: 0.73), spleen index (AUROC: 0.70), spleen transverse diameter ratio (AUROC: 0.71), and spleen index ratio (AUROC: 0.72) in predicting venous complications were higher than other ones. CONCLUSIONS: Ultrasonic examination is a common follow-up method for pediatric patients after liver transplantation and the application of ultrasonic spleen parameters may be helpful to monitor venous complications.


Asunto(s)
Trasplante de Hígado , Bazo , Humanos , Niño , Bazo/diagnóstico por imagen , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Estudios Retrospectivos , Vena Porta/diagnóstico por imagen , Ultrasonografía , Vena Esplénica/diagnóstico por imagen
3.
Angew Chem Int Ed Engl ; 63(14): e202400103, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38230920

RESUMEN

Strained macrocycles display interesting properties, such as conformational rigidity, often resulting in enhanced π-conjugation or enhanced affinity for non-covalent guest binding, yet they can be difficult to synthesize. Here we use computational modeling to design a template to direct the formation of an 18-porphyrin nanoring with direct meso-meso bonds between the porphyrin units. Coupling of a linear 18-porphyrin oligomer in the presence of this template gives the target nanoring, together with an unexpected 36-porphyrin ring by-product. Scanning tunneling microscopy (STM) revealed the elliptical conformations and flexibility of these nanorings on a Au(111) surface.

4.
J Am Chem Soc ; 145(28): 15265-15274, 2023 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-37417934

RESUMEN

Since the early days of quantum mechanics, it has been known that electrons behave simultaneously as particles and waves, and now quantum electronic devices can harness this duality. When devices are shrunk to the molecular scale, it is unclear under what conditions does electron transmission remain phase-coherent, as molecules are usually treated as either scattering or redox centers, without considering the wave-particle duality of the charge carrier. Here, we demonstrate that electron transmission remains phase-coherent in molecular porphyrin nanoribbons connected to graphene electrodes. The devices act as graphene Fabry-Pérot interferometers and allow for direct probing of the transport mechanisms throughout several regimes. Through electrostatic gating, we observe electronic interference fringes in transmission that are strongly correlated to molecular conductance across multiple oxidation states. These results demonstrate a platform for the use of interferometric effects in single-molecule junctions, opening up new avenues for studying quantum coherence in molecular electronic and spintronic devices.

5.
J Dairy Sci ; 106(10): 6731-6740, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37210347

RESUMEN

Brown fermented milk (BFM) is favored by consumers in the dairy market for its unique burnt flavor and brown color. However, Maillard reaction products (MRP) from high-temperature baking are also noteworthy. In this study, tea polyphenols (TP) were initially developed as potential inhibitors of MRP formation in BFM. The results showed that the flavor profile of BFM did not change after adding 0.08% (wt/wt) of TP, and its inhibition rates on 5-hydroxymethyl-2-furaldehyde (5-HMF), glyoxal (GO), methylglyoxal (MGO), Nε-carboxymethyl lysine (CML), and Nε-carboxyethyl lysine (CEL) were 60.8%, 27.12%, 23.44%, 57.7%, and 31.28%, respectively. After 21 d of storage, the levels of 5-HMF, GO, MGO, CML, and CEL in BFM with TP were 46.3%, 9.7%, 20.6%, 5.2%, and 24.7% lower than the control group, respectively. Moreover, a smaller change occurred in their color and the browning index was lower than that of the control group. The significance of this study was to develop TP as additives to inhibit the production of MRP in brown fermented yogurt without changing color and flavors, thereby making dairy products safer for consumers.


Asunto(s)
Reacción de Maillard , Leche , Animales , Leche/química , Lisina/análisis , Polifenoles/análisis , Óxido de Magnesio , Piruvaldehído/análisis , Glioxal/análisis , Productos Finales de Glicación Avanzada/análisis ,
6.
Lasers Med Sci ; 38(1): 265, 2023 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-37973668

RESUMEN

Photobiomodulation (PBM) has been emerging as a promising alternative therapy in dentistry. However, various parameters of PBM are used in different studies, and there is limited cumulative data on PBM for improving bone formation in clinical trials. The aim of this review was to evaluate the effectiveness of PBM in the process of bone remodeling in dentistry using randomized controlled trials. Initially, a total of 1,011 articles published from January 2008 to December 2021 were retrieved from five electronic databases (PubMed, Scopus, Cochrane Library, EMBASE, and CINAHL). After a two-step review, nine articles met the inclusion criteria. The parameter of PBM, group, treatment sessions, assessment times and outcomes of the included studies were reviewed. Eighty-nine percent of the studies revealed positive effects on bone formation between the laser group and the control group. Only one article reported that light-emitting diode did not significantly enhance osteogenesis. Additionally, the present study shows that Gallium aluminum arsenide of near infrared (NIR) laser with continuous mode is the most commonly used form of PBM. The biostimulatory effects are dependent on several parameters, with wavelength and dose being more important than others. Based on this review, it is suggested that the NIR range and an appropriate dose of PBM could be used to increase the efficiency of stimulating bone healing and remodeling. However, standardization of treatment protocols is needed to clarify therapeutic strategies in dentistry.


Asunto(s)
Terapia por Luz de Baja Intensidad , Terapia por Luz de Baja Intensidad/métodos , Osteogénesis , Luz , Remodelación Ósea , Odontología
7.
Analyst ; 147(15): 3570-3577, 2022 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-35816051

RESUMEN

Lipid droplets (LDs) have emerged as a hot target for cancer therapeutics in recent years owing to findings that have shown them to be key organelles involved in maintaining cellular stability and regulating inter-organelle communication through molecular trafficking. LDs emerge from the endoplasmic reticulum (ER) as a form of cellular homeostasis control. We herein report the study of a library of asymmetric squaraines as superior fluorescence probes to track and image LDs in their native state and environment within cancer cells. The probes are highly selective towards LDs and displayed prominent bright fluorescence with just 1 µM probe concentration. They also possess bimodal LD and ER staining capability via the simple diffusion of small lipophilic molecules. The probes almost instantly stained LDs, while the ER staining rate is dependent on the probe's lipophilicity and the incubation duration. These "on-demand" organelle-selective probes are highly desirable tools for revealing the role of LDs in governing many cellular processes, especially in malignant cells.


Asunto(s)
Gotas Lipídicas , Supervivencia Celular , Ciclobutanos , Retículo Endoplásmico/metabolismo , Gotas Lipídicas/metabolismo , Imagen Molecular , Fenoles , Coloración y Etiquetado
8.
Angew Chem Int Ed Engl ; 61(36): e202201231, 2022 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-35818688

RESUMEN

A recent Research Article in this journal by Matito and co-workers claimed that none of the oxidation states of a butadiyne-linked six-porphyrin nanoring exhibit global aromaticity or antiaromaticity. Here we show that this conclusion is incorrect. Experimental data from NMR spectroscopy for a whole family of nanorings provide strong evidence for global ring currents. The NMR data reveal these ring currents directly, without needing analysis by density functional theory (DFT). Furthermore, DFT calculations reproduce the experimental results when a suitable functional is used.

9.
Org Biomol Chem ; 19(39): 8507-8515, 2021 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-34542126

RESUMEN

Quinoliziniums, cationic aromatic heterocycles bearing a quaternary bridgehead nitrogen, have been widely used as fluorescent dyes, DNA intercalators, ionic liquids etc. A library of new quinolizinium compounds was synthesized from quinolines and internal alkyne substrates in up to 65% isolated yields. Systematic studies of their photophysical properties were conducted. The quinoliziniums have been used in three visible-light-induced photocatalysis reactions with good yields.


Asunto(s)
Sustancias Intercalantes
10.
Appl Microbiol Biotechnol ; 105(2): 869-876, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33404828

RESUMEN

Recent attempts to create synthetic Escherichia coli methylotrophs identified that de novo biosynthesis of amino acids, in the presence of methanol, presents significant challenges in achieving autonomous methylotrophic growth. Previously engineered methanol-dependent strains required co-utilization of stoichiometric amounts of co-substrates and methanol. As such, these strains could not be evolved to grow on methanol alone. In this work, we have explored an alternative approach to enable biosynthesis of all amino acids from methanol-derived carbon in minimal media without stoichiometric coupling. First, we identified that biosynthesis of threonine was limiting the growth of our methylotrophic E. coli. To address this, we performed adaptive laboratory evolution to generate a strain that grew efficiently in minimal medium with methanol and threonine. Methanol assimilation and growth of the evolved strain were analyzed, and, interestingly, we found that the evolved strain synthesized all amino acids, including threonine, from methanol-derived carbon. The evolved strain was then further engineered through overexpression of an optimized threonine biosynthetic pathway. We show that the resulting methylotrophic E. coli strain has a methanol-dependent growth phenotype with homoserine as co-substrate. In contrast to previous methanol-dependent strains, co-utilization of homoserine is not stoichiometrically linked to methanol assimilation. As such, future engineering of this strain and successive adaptive evolution could enable autonomous growth on methanol as the sole carbon source. KEY POINTS: • Adaptive evolution of E. coli enables biosynthesis of all amino acids from methanol. • Overexpression of threonine biosynthesis pathway improves methanol assimilation. • Methanol-dependent growth is seen in minimal media with homoserine as co-substrate.


Asunto(s)
Escherichia coli , Metanol , Aminoácidos , Carbono , Escherichia coli/genética , Laboratorios
11.
J Am Chem Soc ; 142(45): 19393-19401, 2020 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-33125228

RESUMEN

Template-directed synthesis has been used to prepare a fully π-conjugated cyclic porphyrin octamer, composed of both ß,meso,ß-edge-fused porphyrin tape units and butadiyne-linked porphyrins. The UV-vis-NIR spectra of this partially fused nanoring show that π-conjugation extends around the whole macrocycle, and that it has a smaller HOMO-LUMO gap than its all-butadiyne-linked analogue, as predicted by TD-DFT calculations. The 1H NMR shifts of the bound templates confirm the disrupted aromaticity of the edge-fused porphyrins in the neutral nanoring. NMR oxidation titrations reveal the presence of a global paratropic ring current in its 4+ and 8+ oxidation states and of a global diatropic ring current in the 6+ state of the partially fused ring. The paratropic ring current in the 4+ oxidation state is about four times stronger than that in the all-butadiyne-linked cyclic octamer complex, whereas the diatropic current in the 6+ state is about 40% weaker. Two isomeric K-shaped tetrapyridyl templates with trifluoromethyl substituents at different positions were used to probe the distribution of the ring current in the 4+, 6+, and 8+ oxidation states by 19F NMR, demonstrating that the ring currents are global and homogeneous.

12.
BMC Plant Biol ; 20(1): 410, 2020 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-32883206

RESUMEN

BACKGROUND: To fully elucidate the roles and mechanisms of plant hormones in leaf senescence, we adopted an integrated analysis of both non-senescing and senescing leaves from red maple with transcriptome and metabolome data. RESULTS: Transcription and metabolite profiles were generated through a combination of deep sequencing, third-generation sequencing data analysis, and ultrahigh-performance liquid chromatograph Q extractive mass spectrometry (UHPLC-QE-MS), respectively. We investigated the accumulation of compounds and the expression of biosynthesis and signaling genes for eight hormones. The results revealed that ethylene and abscisic acid concentrations increased during the leaf senescence process, while the contents of cytokinin, auxin, jasmonic acid, and salicylic acid continued to decrease. Correlation tests between the hormone content and transcriptional changes were analyzed, and in six pathways, genes closely linked with leaf senescence were identified. CONCLUSIONS: These results will enrich our understanding of the mechanisms of plant hormones that regulate leaf senescence in red maple, while establishing a foundation for the genetic modification of Acer in the future.


Asunto(s)
Acer/genética , Redes y Vías Metabólicas , Metaboloma , Reguladores del Crecimiento de las Plantas/metabolismo , Hojas de la Planta/crecimiento & desarrollo , Transcriptoma , Acer/crecimiento & desarrollo , Acer/metabolismo , Perfilación de la Expresión Génica , Redes y Vías Metabólicas/genética , Metabolómica , Reguladores del Crecimiento de las Plantas/genética , Hojas de la Planta/genética , Transcripción Genética
13.
Metab Eng ; 57: 247-255, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31881281

RESUMEN

Escherichia coli is an ideal choice for constructing synthetic methylotrophs capable of utilizing the non-native substrate methanol as a carbon and energy source. All current E. coli-based synthetic methylotrophs require co-substrates. They display variable levels of methanol-carbon incorporation due to a lack of native regulatory control of biosynthetic pathways, as E. coli does not recognize methanol as a proper substrate despite its ability to catabolize it. Here, using the E. coli formaldehyde-inducible promoter Pfrm, we implement dynamic expression control of select pentose-phosphate genes in response to the formaldehyde produced upon methanol oxidation. Genes under Pfrm control exhibited 8- to 30-fold transcriptional upregulation during growth on methanol. Formaldehyde-induced episomal expression of the B. methanolicus rpe and tkt genes involved in the regeneration of ribulose 5-phosphate required for formaldehyde fixation led to significantly improved methanol assimilation into intracellular metabolites, including a 2-fold increase of 13C-methanol into glutamate. Using a simple strategy for redox perturbation by deleting the E. coli NAD-dependent malate dehydrogenase gene maldh, we demonstrate 5-fold improved biomass formation of cells growing on methanol in the presence of a small concentration of yeast extract. Further improvements in methanol utilization are achieved via adaptive laboratory evolution and heterologous rpe and tkt expression. A short-term in vivo13C-methanol labeling assay was used to determine methanol assimilation activity for Δmaldh strains, and demonstrated dramatically higher labeling in intracellular metabolites, including a 6-fold and 1.8-fold increase in glycine labeling for the rpe/tkt and evolved strains, respectively. The combination of formaldehyde-controlled pentose phosphate pathway expression and redox perturbation with the maldh knock-out greatly improved both growth benefit with methanol and methanol carbon incorporation into intracellular metabolites.


Asunto(s)
Escherichia coli , Formaldehído/metabolismo , Regulación Bacteriana de la Expresión Génica , Ingeniería Metabólica , Microorganismos Modificados Genéticamente , Vía de Pentosa Fosfato/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Ácido Glutámico/biosíntesis , Ácido Glutámico/genética , Metanol/metabolismo , Microorganismos Modificados Genéticamente/genética , Microorganismos Modificados Genéticamente/metabolismo
14.
Metab Eng ; 61: 1-10, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32360074

RESUMEN

Synthetic methylotrophy aims to engineer methane and methanol utilization pathways in platform hosts like Escherichia coli for industrial bioprocessing of natural gas and biogas. While recent attempts to engineer synthetic methylotrophs have proved successful, autonomous methylotrophy, i.e. the ability to utilize methane or methanol as sole carbon and energy substrates, has not yet been realized. Here, we address an important limitation of autonomous methylotrophy in E. coli: the inability of the organism to synthesize several amino acids when grown on methanol. By activating the stringent/stress response via ppGpp overproduction, or DksA and RpoS overexpression, we demonstrate improved biosynthesis of proteinogenic amino acids via endogenous upregulation of amino acid synthesis pathway genes. Thus, we were able to achieve biosynthesis of several limiting amino acids from methanol-derived carbon, in contrast to the control methylotrophic E. coli strain. This study addresses a key limitation currently preventing autonomous methylotrophy in E. coli and possibly other synthetic methylotrophs and provides insight as to how this limitation can be alleviated via stringent/stress response activation.


Asunto(s)
Proteínas Bacterianas , Proteínas de Escherichia coli , Escherichia coli , Regulación Bacteriana de la Expresión Génica , Metanol/metabolismo , Factor sigma , Proteínas Bacterianas/biosíntesis , Proteínas Bacterianas/genética , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/biosíntesis , Proteínas de Escherichia coli/genética , Factor sigma/biosíntesis , Factor sigma/genética
15.
Metab Eng ; 60: 45-55, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32179162

RESUMEN

Synthetic methylotrophy aims to engineer methane and methanol utilization pathways in platform hosts like Escherichia coli for industrial bioprocessing of natural gas and biogas. While recent attempts to engineer synthetic methanol auxotrophs have proved successful, these studies focused on scarce and expensive co-substrates. Here, we engineered E. coli for methanol-dependent growth on glucose, an abundant and inexpensive co-substrate, via deletion of glucose 6-phosphate isomerase (pgi), phosphogluconate dehydratase (edd), and ribose 5-phosphate isomerases (rpiAB). Since the parental strain did not exhibit methanol-dependent growth on glucose in minimal medium, we first achieved methanol-dependent growth via amino acid supplementation and used this medium to evolve the strain for methanol-dependent growth in glucose minimal medium. The evolved strain exhibited a maximum growth rate of 0.15 h-1 in glucose minimal medium with methanol, which is comparable to that of other synthetic methanol auxotrophs. Whole genome sequencing and 13C-metabolic flux analysis revealed the causative mutations in the evolved strain. A mutation in the phosphotransferase system enzyme I gene (ptsI) resulted in a reduced glucose uptake rate to maintain a one-to-one molar ratio of substrate utilization. Deletion of the e14 prophage DNA region resulted in two non-synonymous mutations in the isocitrate dehydrogenase (icd) gene, which reduced TCA cycle carbon flux to maintain the internal redox state. In high cell density glucose fed-batch fermentation, methanol-dependent acetone production resulted in 22% average carbon labeling of acetone from 13C-methanol, which far surpasses that of the previous best (2.4%) found with methylotrophic E. coli Δpgi. This study addresses the need to identify appropriate co-substrates for engineering synthetic methanol auxotrophs and provides a basis for the next steps toward industrial one-carbon bioprocessing.


Asunto(s)
Escherichia coli/crecimiento & desarrollo , Escherichia coli/metabolismo , Glucosa/metabolismo , Ingeniería Metabólica/métodos , Metanol/metabolismo , Biomasa , Ciclo del Ácido Cítrico , Proteínas de Escherichia coli/genética , Eliminación de Gen , Glucosa-6-Fosfato Isomerasa/genética , Glucosa-6-Fosfato Isomerasa/metabolismo , Isocitrato Deshidrogenasa/metabolismo , Profagos/genética
16.
Bioorg Med Chem ; 28(7): 115375, 2020 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-32122753

RESUMEN

Alkyne is a useful functionality incorporated in proteins for site-selective bioconjugation reactions. Although effective bioconjugation reactions such as copper(I)-catalyzed and/or copper-free 1,3-dipolar cycloadditions of alkynes and azides are the most common approaches, the development of new alkyne-based bioconjugation reactions is still an ongoing interest in chemical biology. In this work, a new approach has been developed for selective modification of alkyne-linked peptides and proteins through the formation of arylacetylenes by a cross-coupling reaction of 6-membered ring cyclometalated gold(III) (C^N) complexes (HC^N = 2-arylpyridines) with terminal alkynes. Screening of the reaction conditions with a series of cyclometalated gold(III) complexes with phenylacetylene gave an excellent yield (up to 82%) by conducting the reaction in slightly alkaline aqueous conditions. The reaction scope was expanded to various alkynes, including alkyne-linked peptides to achieve up to >99% conversion. Using fluorescent dansyl (1l) and BODIPY (1m)-linked gold(III) complexes, alkyne-linked lysozyme has been selectively modified.


Asunto(s)
Oro/química , Compuestos Organometálicos/síntesis química , Péptidos/química , Proteínas/química , Alquinos/química , Catálisis , Reacción de Cicloadición , Estructura Molecular , Compuestos Organometálicos/química
17.
Zhongguo Zhong Yao Za Zhi ; 45(22): 5383-5392, 2020 Nov.
Artículo en Zh | MEDLINE | ID: mdl-33350197

RESUMEN

Hypertension is a kind of chronic cardiovascular system disease caused by a series of factors and carriers dysfunction, which belongs to the category of Tibetan medicine "Chalong disease", and has a high rate of disability and mortality. Zuomua Decoction is a classical Tibetan medicine for Chalong disease, but its mechanism is not clear. Therefore, in this paper we explored the multi-components, multi-targets and multi-channels mechanism of Zuomua Decoction in the treatment of hypertension based on network pharmacology and molecular docking technology. First of all, the chemical components of Zuomua Decoction were obtained in the retrieval of traditional Chinese medicine systems pharmacology database(TCMSP), China National Knowledge Infrastructure(CNKI) and Wanfang database. The potential targets of Zuomua Decoction were predicted by BATMAN-TCM database, and the targets of hypertension were obtained by using DisGeNET database. The intersection of these two targets set was taken to obtain the potential targets of Zuomua Decoction in the treatment of hypertension, and then the chemical compositions-targets network was constructed. Secondly, the intersection targets were imported into STRING database to obtain the interaction relationship of intersection targets, and the protein interaction network of Zuomua Decoction in the treatment of hypertension was constructed in Cytoscape. Topological, GO, and KEGG enrichment analysis were used to construct the key targets-signal pathways-biological processes network diagram and explore the mechanism of Zuomua Decoction in the treatment of hypertension. Finally, the key targets were selected to construct the pharmacodynamic identification models to verify the effect mode of Zomua Decoction in treating hypertension. The results showed that there were 61 chemical components and 90 potential targets in the compounds-targets network. We obtained 21 key targets, 154 signal pathways, and 382 biological processes in topological, GO, and KEGG enrichment analysis of the protein interaction network, and in the comprehensive analysis, it was found that Zuomua Decoction could reduce blood pressure by regulating renin angiotension aldosterone system, balancing the concentration of intracellular calcium and sodium ions and regulating vasoconstriction and relaxation. ACE, AGTR1, and ADRB2 were used as the carriers for molecular docking study on the components of Zuoma Decoction, and the results showed that the chemical components of Zuomua Decoction had a good binding activity with key targets. The purpose of this study is to provide ideas for the in-depth study of Zuoma Decoction in the treatment of hypertension, and provide scientific basis for its clinical rational application.


Asunto(s)
Medicamentos Herbarios Chinos , Hipertensión , Antihipertensivos , China , Humanos , Hipertensión/tratamiento farmacológico , Medicina Tradicional Tibetana , Simulación del Acoplamiento Molecular , Tecnología
18.
Clin Immunol ; 193: 60-69, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29410331

RESUMEN

Bladder cancer (BC) is a disease arising from the malignant cells of the urinary bladder. Myeloid-derived suppressor cells (MDSCs) expand broadly and have strong immunosuppressive activities in the cancer microenvironment. Determining how to inhibit the negative effects of MDSCs requires immediate attention. In this study, we found that granulocytic-MDSCs (G-MDSCs), which constitute one of the two types of MDSCs, were significantly increased in BC tissues compared with those in the adjacent bladder tissues. There was a robust negative correlation between the G-MDSCs and the CD8+ T cells in the BC tissues. In this study, we attempted to identify pharmacological approaches to eliminate MDSCs and restore T cell anti-tumor activities. It is necessary to explore a method to eliminate the detrimental effects of MDSCs. Cisplatin, a chemotherapy medication used to treat BC, not only rapidly kills proliferating cancer cells but also affects the tumor immune microenvironment. However, the mechanism underlying this phenomenon is largely unknown. In this study, we found that Cisplatin directly inhibited the proliferation and induced the apoptosis of T24 cells (a BC cell line), as well as decreased the percentage of the G-MDSCs in the population of peripheral blood mononuclear cells (PBMCs), which restored the expansion of the CD8+ T cells. In the C3H/He mouse BC model, Cisplatin treatment inhibited the progression of BC and effectively decreased the proportion of G-MDSCs. These results suggest that Cisplatin treatment enhances the anti-tumor function of CD8+ T cells by decreasing G-MDSCs. This finding provides a new perspective for Cisplatin treatment to prevent the progression of BC, particularly in patients with abnormally high levels of G-MDSCs.


Asunto(s)
Antineoplásicos/uso terapéutico , Linfocitos T CD8-positivos/inmunología , Cisplatino/uso terapéutico , Granulocitos/fisiología , Células Supresoras de Origen Mieloide/fisiología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Antígeno CD11b/metabolismo , Línea Celular Tumoral , Modelos Animales de Enfermedad , Femenino , Granulocitos/efectos de los fármacos , Humanos , Masculino , Ratones , Ratones Endogámicos C3H , Persona de Mediana Edad , Células Supresoras de Origen Mieloide/efectos de los fármacos , Microambiente Tumoral , Neoplasias de la Vejiga Urinaria/inmunología
19.
Angew Chem Int Ed Engl ; 56(11): 3074-3079, 2017 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-28165658

RESUMEN

Unprecedented stable BINOL/gold(III) complexes, adopting a novel C,O-chelation mode, were synthesized by a modular approach through combination of 1,1'-binaphthalene-2,2'-diols (BINOLs) and cyclometalated gold(III) dichloride complexes [(C^N)AuCl2 ]. X-ray crystallographic analysis revealed that the bidentate BINOL ligands tautomerized and bonded to the AuIII atom through C,O-chelation to form a five-membered ring instead of the conventional O,O'-chelation giving a seven-membered ring. These gold(III) complexes catalyzed acetalization/cycloisomerization and carboalkoxylation of ortho-alkynylbenzaldehydes with trialkyl orthoformates.

20.
J Fluoresc ; 26(4): 1239-48, 2016 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27165037

RESUMEN

Steroid ligands can easily diffuse through the cell membrane and this property makes it feasible to be used for in-situ staining of the nuclear receptors. However, nonspecific binding of the internalized ligand probe with the cellular components has caused serious interferences for the detection of receptor-expressing cells. We report a novel gold nanocluster (AuNC)-conjugated estrogen probe that can eliminate nonspecific internalization and accelerate nuclear localization to achieve selective and rapid detection of estrogen receptors (ERs) in live cells. The AuNC, protected by bovine serum albumin (BSA), BSA-AuNCs, was prepared by the synthesis and confirmed to be 1.9 nm in core size and 18 nm in diameter. Ethinyl estradiol was used as the precursor of 17ß-estradial (E2) to conjugate with BSA-protected AuNCs via polyethylene glycol linker (E2-PEG/BSA-AuNCs) or to conjugate with Cy3 dyes (E2-Cy3). The conjugated probe was determined to contain five E2 molecules per BSA-AuNC by mass spectrometry and exhibit an emission maximum of around 640 nm, which was not altered by E2 conjugation indicating that the structural integrity of BSA-AuNCs was conserved. E2-PEG/BSA-AuNCs probes were quickly internalized by MCF-7 (ER+) cells and localized to the nuclei in 2 h. Such internalization was sensitive to competition by free E2 and was rarely detected in the controls using either non-conjugated BSA-AuNCs in MCF-7 (ER+) cells or E2-PEG/BSA-AuNCs in MDA-MB-231 (ER-) cells. In contrast to the high specificity of E2-PEG/BSA-AuNCs probe, the uptake of E2-Cy3 probe could not differentiate between MCF-7(ER+) and MDA-MB-231(ER-) cells during the early phases of the treatment. Moreover, nuclear targeting by E2-Cy3 was three times slower than that by the E2-PEG/BSA-AuNC probe. Such accelerated nuclei targeting was consistent with the enhanced cell viability by conjugating E2 with BSA-AuNC. In conclusion, the E2-PEG/BSA-AuNC probes are promising candidates that can be used for the detection of ER+ tumor tissues and the same strategy can be applied to fabricate other steroid probes.


Asunto(s)
Estradiol/química , Oro/química , Nanopartículas del Metal/química , Imagen Óptica/métodos , Receptores de Estrógenos/metabolismo , Albúmina Sérica Bovina/química , Alquinos/química , Animales , Transporte Biológico , Carbocianinas/química , Bovinos , Supervivencia Celular , Química Clic , Estradiol/metabolismo , Etinilestradiol/química , Humanos , Células MCF-7
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