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1.
Exp Cell Res ; 442(1): 114198, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39103071

RESUMEN

Macrophages play crucial roles in the tumor microenvironment (TME), exerting diverse functions ranging from promoting tumor growth and metastasis to orchestrating anti-tumor immune responses. Their plasticity allows them to adopt distinct activation states, often called M1-like (pro-inflammatory) and M2-like (anti-inflammatory or pro-tumoral), significantly influencing tumor progression and response to therapy. Harnessing the potential of macrophages in cancer immunotherapy has emerged as a promising strategy, with increasing interest in targeting these cells directly or modulating their functions within the TME. This review explores the intricate interplay between macrophages, the TME, and immunotherapeutic approaches. We discuss the dynamic phenotypic and functional heterogeneity of tumor-associated macrophages (TAMs), their impact on disease progression, and the mechanisms underlying their response to immunotherapy. Furthermore, we highlight recent advancements in macrophage-based immunotherapeutic strategies, including macrophage-targeting agents, adoptive cell transfer, and engineering approaches. Understanding the complex crosstalk between macrophages and the TME is essential for developing effective immunotherapeutic interventions that exploit the immunomodulatory functions of macrophages to enhance anti-tumor immunity and improve clinical outcomes for cancer patients.


Asunto(s)
Inmunoterapia , Macrófagos , Neoplasias , Microambiente Tumoral , Humanos , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/patología , Inmunoterapia/métodos , Microambiente Tumoral/inmunología , Macrófagos/inmunología , Animales , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo
2.
J Am Chem Soc ; 146(36): 24832-24841, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39145670

RESUMEN

Light presents substantial potential in disease treatment, where the development of efficient photocatalysts could enhance the utilization of photocatalytic systems in biomedicine. Here, we devised a novel approach to designing and synthesizing photocatalysts of conjugated polymers for photocatalytic CO2 reduction, relying on a multiple linear regression model built with theoretically calculated descriptors. We established a logarithmic relationship between molecular structure and CO yield and identified the poly(fluorene-co-thiophene) deviant (PFT) as the optimal one. PFT excited a CO regeneration ratio of 231 nmol h-1 in acetonitrile and 46 nmol h-1 in an aqueous solution with a reaction selectivity of 88%. Further advancements were made through the development of liposomes encapsulating PFT for targeted macrophage delivery. By distributing PFT on the liposome membranes, our constructed photocatalytic system efficiently generated CO in situ from surrounding CO2. This localized CO production served as an endogenous signaling molecule, promoting the desirable polarization of macrophages from the M1 to M2 phenotype. Consequently, the M2 cells reduced the secretion of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß). We also demonstrated the efficacy of our system in treating lipopolysaccharide-induced inflammation of cardiomyocytes under white light irradiation. Moreover, our research provides a comprehensive understanding of the intricate processes involved in CO2 reduction by a combination of theoretical calculations and experimental techniques including transient absorption, femtosecond ultrafast spectroscopy, and in situ infrared spectroscopy. These findings pave the way for further advancements of conjugated polymers and photocatalytic systems in biomedical investigation.


Asunto(s)
Dióxido de Carbono , Monóxido de Carbono , Macrófagos , Procesos Fotoquímicos , Polímeros , Dióxido de Carbono/química , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Polímeros/química , Monóxido de Carbono/química , Catálisis , Ratones , Animales , Células RAW 264.7 , Oxidación-Reducción , Estructura Molecular
3.
J Am Chem Soc ; 146(36): 25383-25393, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39196894

RESUMEN

The regulation of the cell membrane potential plays a crucial role in governing the transmembrane transport of various ions and cellular life processes. However, in situ and on-demand modulation of cell membrane potential for ion channel regulation is challenging. Herein, we have constructed a supramolecular assembly system based on water-soluble cationic oligo(phenylenevinylene) (OPV) and cucurbit[7]uril (CB[7]). The controllable disassembly of OPV/4CB[7] combined with the subsequent click reaction provides a step-by-step adjustable surface positive potential. These processes can be employed in situ on the plasma membrane to modulate the membrane potential on-demand for precisely controlling the activation of the transient receptor potential vanilloid 1 (TRPV1) ion channel and up-regulating exogenous calcium-responsive gene expression. Compared with typical optogenetics, electrogenetics, and mechanogenetics, our strategy provides a perspective supramolecular genetics toolbox for the regulation of membrane potential and downstream intracellular gene regulation events.


Asunto(s)
Imidazoles , Potenciales de la Membrana , Imidazoles/química , Humanos , Hidrocarburos Aromáticos con Puentes/química , Polivinilos/química , Membrana Celular/metabolismo , Membrana Celular/química , Canales Catiónicos TRPV/metabolismo , Células HEK293 , Calcio/metabolismo , Calcio/química , Canales de Calcio/metabolismo , Canales de Calcio/química , Compuestos Heterocíclicos con 2 Anillos , Compuestos Macrocíclicos , Imidazolidinas
4.
Small ; 20(8): e2306440, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37840382

RESUMEN

The development of artificial photosynthesis systems that mimics natural photosynthesis can help address the issue of energy scarcity by efficiently utilizing solar energy. Here, it presents liposomes-based artificial photosynthetic nanocapsules (PSNC) integrating photocatalytic, chemical catalytic, and biocatalytic systems through one-pot method. The PSNC contains 5,10,15,20-tetra(4-pyridyl) cobalt-porphyrin, tridipyridyl-ruthenium nitrate, oligo-pphenyl-ethylene-rhodium complex, and creatine kinase, efficiently generating oxygen, nicotinamide adenine dinucleotide (NADH), and adenosine triphosphate with remarkable enhancements of 231%, 30%, and 86%, compared with that of molecules mixing in aqueous solution. Additionally, the versatile PSNC enables simulation of light-independent reactions, achieving a controllable output of various target products. The regenerated NADH within PSNC further facilitates alcohol dehydrogenase, yielding methanol with a notable efficiency improvement of 37%. This work introduces a promising platform for sustainable solar energy conversion and the simultaneous synthesis of multiple valuable products in an ingenious and straightforward way.


Asunto(s)
NAD , Energía Solar , Fotosíntesis , Luz Solar , Liposomas
5.
J Cardiovasc Pharmacol ; 84(2): 136-145, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38922572

RESUMEN

ABSTRACT: This review summarizes the multiple roles of microRNAs (miRNAs) in the prediction and treatment of heart failure (HF), including the molecular mechanisms regulating cell apoptosis, myocardial fibrosis, cardiac hypertrophy, and ventricular remodeling, and highlights the importance of miRNAs in the prognosis of HF. In addition, the strategies for alleviating HF with miRNA intervention are discussed. On the basis of the challenges and emerging directions in the research and clinical practice of HF miRNAs, it is proposed that miRNA-based therapy could be a new approach for prevention and treatment of HF.


Asunto(s)
Apoptosis , Insuficiencia Cardíaca , MicroARNs , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/diagnóstico , Animales , Remodelación Ventricular/genética , Fibrosis , Terapia Genética/métodos , Regulación de la Expresión Génica , Marcadores Genéticos , Transducción de Señal , Miocardio/metabolismo , Miocardio/patología , Pronóstico
6.
Bioorg Chem ; 145: 107188, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38377815

RESUMEN

Despite the advances of multistep enzymatic cascade reactions, their incorporation with abiotic reactions in living organisms remains challenging in synthetic biology. Herein, we combined microbial metabolic pathways and Pd-catalyzed processes for in-situ generation of bioactive conjugated oligomers. Our biocompatible one-pot coupling reaction utilized the fermentation process of engineered E. coli that converted glucose to styrene, which participated in the Pd-catalyzed Heck reaction for in-situ synthesis of conjugated oligomers. This process serves a great interest in understanding resistance evolution by utilizing the inhibitory activity of the synthesized conjugated oligomers. The approach allows for the in-situ combination of biological metabolism and CC coupling reactions, opening up new possibilities for the biosynthesis of unnatural molecules and enabling the in-situ regulation of the bioactivity of the obtained products.


Asunto(s)
Escherichia coli , Paladio , Escherichia coli/metabolismo , Catálisis , Fermentación
7.
Sensors (Basel) ; 24(11)2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38894174

RESUMEN

A Cable-Driven Continuum Robot (CDCR) that consists of a set of identical Cable-Driven Continuum Joint Modules (CDCJMs) is proposed in this paper. The CDCJMs merely produce 2-DOF bending motions by controlling driving cable lengths. In each CDCJM, a pattern-based flexible backbone is employed as a passive compliant joint to generate 2-DOF bending deflections, which can be characterized by two joint variables, i.e., the bending direction angle and the bending angle. However, as the bending deflection is determined by not only the lengths of the driving cables but also the gravity and payload, it will be inaccurate to compute the two joint variables with its kinematic model. In this work, two stretchable capacitive sensors are employed to measure the bending shape of the flexible backbone so as to accurately determine the two joint variables. Compared with FBG-based and vision-based shape-sensing methods, the proposed method with stretchable capacitive sensors has the advantages of high sensitivity to the bending deflection of the backbone, ease of implementation, and cost effectiveness. The initial location of a stretchable sensor is generally defined by its two endpoint positions on the surface of the backbone without bending. A generic shape-sensing model, i.e., the relationship between the sensor reading and the two joint variables, is formulated based on the 2-DOF bending deflection of the backbone. To further improve the accuracy of the shape-sensing model, a calibration method is proposed to compensate for the location errors of stretchable sensors. Based on the calibrated shape-sensing model, a sliding-mode-based closed-loop control method is implemented for the CDCR. In order to verify the effectiveness of the proposed closed-loop control method, the trajectory tracking accuracy experiments of the CDCR are conducted based on a circle trajectory, in which the radius of the circle is 55mm. The average tracking errors of the CDCR measured by the Qualisys motion capture system under the open-loop and the closed-loop control are 49.23 and 8.40mm, respectively, which is reduced by 82.94%.

8.
Angew Chem Int Ed Engl ; : e202406527, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39137101

RESUMEN

Photosynthetic microorganisms, which rely on light-driven electron transfer, store solar energy in self-energy carriers and convert it into bioenergy. Although these microorganisms can operate light-induced charge separation with nearly 100% quantum efficiency, their practical applications are inherently limited by the photosynthetic energy conversion efficiency. Artificial semiconductors can induce an electronic response to photoexcitation, providing additional excited electrons for natural photosynthesis to improve solar conversion efficiency. However, challenges remain in importing exogenous electrons across cell membranes. In this work, we have developed an engineered gold nanocluster/organic semiconductor heterostructure (AuNC@OFTF) to couple the intracellular electron transport chain of living cyanobacteria. AuNC@OFTF exhibits a prolonged excited state lifetime and effective charge separation. The internalized AuNC@OFTF permits its photogenerated electrons to participate in the downstream of photosystem II and construct an oriented electronic highway, which enables a five-fold increase in photocurrent in living cyanobacteria. Moreover, the binding events of AuNC@OFTF established an abiotic-biotic electronic interface at the thylakoid membrane to enhance electron flux and finally furnished nicotinamide adenine dinucleotide phosphate. Thus, AuNC@OFTF can be exploited to spatiotemporally manipulate and enhance the solar conversion of living cyanobacteria in cells, providing an extended nanotechnology for re-engineering photosynthetic pathways.

9.
Small ; 19(48): e2303035, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37605329

RESUMEN

Engineered nanomaterials hold great promise to improve the specificity of disease treatment. Herein, a fully protein-based material is obtained from nonpathogenic Escherichia coli (E. coli), which is capable of morphological transformation from globular to fibrous in situ for inducing tumor cell apoptosis. The protein-based material P1 is comprised of a ß-sheet-forming peptide KLVFF, pro-apoptotic protein BAK, and GFP along with targeting moieties. The self-assembled nanoparticles of P1 transform into nanofibers in situ in the presence of cathepsin B, and the generated nanofibrils favor the dimerization of functional BH3 domain of BAK on the mitochondrial outer membrane, leading to efficient anticancer activity both in vitro and in vivo via mitochondria-dependent apoptosis through Bcl-2 pathway. To precisely manipulate the morphological transformation of biosynthetic molecules in living cells, a spatiotemporally controllable anticancer system is constructed by coating P1-expressing E. coli with cationic conjugated polyelectrolytes to release the peptides in situ under light irradiation. The biosynthetic peptide-based enzyme-catalytic transformation strategy in vivo would offer a novel perspective for targeted delivery and shows great potential in precision disease therapeutics.


Asunto(s)
Escherichia coli , Proteínas Proto-Oncogénicas c-bcl-2 , Escherichia coli/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Apoptosis , Mitocondrias/metabolismo , Membranas Mitocondriales/metabolismo
10.
Acc Chem Res ; 55(2): 156-170, 2022 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-34963291

RESUMEN

Carbon neutrality is increasingly broadly recognized as a vehicle for climate action and sustainable development. Photosynthesis contributes to maintaining a suitable carbon-oxygen balance for survival and plays an irreplaceable role in mitigating the greenhouse effect. However, the energy conversion efficiency of photosynthesis is only about 1%, far below the theoretical maximum. With the ecological demand of carbon neutrality, it is wise and necessary to further improve the efficiency of photosynthesis. Among methods to do so, the most direct and original one is improving the utilization of photosynthetic pigments to the weak absorption region of the spectrum and thus enhancing the solar energy utilization efficiency.This Account summarizes our group's work on constructing conjugated polymer-photosynthetic organism interfaces to augment photosynthetic efficiency. Side chain modification of ionic groups or preparation of nanoparticles makes conjugated polymers water-soluble and electrically charged, which allows them to bind to the surface of photosynthetic microorganisms through electrostatic interactions or be absorbed by plant roots. Owing to the designable and unparalleled light capture and emission capabilities, funnel-like excitation energy transfer mode, and enviable biocompatibility, organic semiconductor conjugated polymers can be used as "artificial antennas" to make up for the lack of natural antenna pigments and expand the photosynthetically active radiation (PAR) range. With this strategy, we achieved enhancement of the photosynthetic efficiency of a broad range of organisms, including oxygenic photosynthetic organisms, from organelle to prokaryotic cyanobacteria, eukaryotic lower plants, and higher plants, as well as anoxygenic photosynthetic organisms. Unlike conventional semiconductors, conjugated polymers have not only electronic conductivity but also ionic conductivity, which is the main means of bioelectrical signal transduction. Therefore, they are able to act as "electron bridges" to accelerate the electron transfer rate at the material-organism interface. On this basis, we introduced conjugated polymers into artificial photosynthesis systems, including biological photovoltaics and artificial carbon sequestration, to increase energy conversion efficiency. These studies open a new frontier for functional studies of conjugated molecules and provide inspirations for the design of photosynthesis systems in the future.


Asunto(s)
Cianobacterias , Energía Solar , Fotosíntesis , Semiconductores , Luz Solar
11.
Zhongguo Zhong Yao Za Zhi ; 48(1): 13-21, 2023 Jan.
Artículo en Zh | MEDLINE | ID: mdl-36725253

RESUMEN

Rheumatoid arthritis(RA) is a chronic degenerative joint disease characterized by inflammation. Due to the complex causes, no specific therapy is available. Non-steroidal anti-inflammatory agents and corticosteroids are often used(long-term, oral/injection) to interfere with related pathways for reducing inflammatory response and delaying the progression of RA, which, however, induce many side effects. Microneedle, an emerging transdermal drug delivery system, is painless and less invasive and improves drug permeability. Thus, it is widely used in the treatment of RA and is expected to be a new strategy in clinical treatment. This paper summarized the application of microneedles in the treatment of RA, providing a reference for the development of new microneedles and the expansion of its clinical application.


Asunto(s)
Artritis Reumatoide , Sistemas de Liberación de Medicamentos , Humanos , Administración Cutánea , Preparaciones Farmacéuticas , Antiinflamatorios no Esteroideos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Agujas
12.
Zhongguo Zhong Yao Za Zhi ; 48(14): 3786-3792, 2023 Jul.
Artículo en Zh | MEDLINE | ID: mdl-37475070

RESUMEN

A fluorescence endoscopic laser confocal microscope(FELCM) was used to direct the injection of sinomenine solid lipid nanoparticles(Sin-SLN) into the joint, and the in vitro effectiveness of Sin-SLN in the treatment of rheumatoid arthritis(RA) was evaluated. Sin-SLN was prepared with the emulsion evaporation-low temperature curing method. The Sin-SLN prepared under the optimal conditions showed the encapsulation efficiency of 64.79%±3.12%, the drug loading of 3.84%±0.28%, the average particle size of(215.27±4.21) nm, and the Zeta potential of(-32.67±0.84) mV. Moreover, the Sin-SLN demonstrated good stability after sto-rage for 30 days. The rabbit model of RA was established by the subcutaneous injection of ovalbumin and complete Freund's adjuvant. Five groups were designed, including a control group, a model group, a Sin(1.5 mg·kg~(-1)) group, a Sin-SLN(1.5 mg·kg~(-1)) group, and a dexamethasone(positive drug, 1.0 mg·kg~(-1), ig) group. The control group and the model group only received puncture treatment without drug injection. After drug administration, the local skin temperature and knee joint diameter were monitored every day. The knee joint diameter and the local skin temperature were lower in the drug administration groups than in the model group(P<0.05, P<0.01). FELCM recorded the morphological alterations of the cartilage of knee joint. The Sin-SLN group showed compact tissue structure and smooth surface of the cartilage. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum le-vels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α). The findings revealed that the Sin-SLN group had lower IL-1 and TNF-α levels than the model group(P<0.05, P<0.01). Hematoxylin-eosin(HE) staining was employed to reveal the pathological changes of the synovial tissue, which were significantly mitigated in the Sin-SLN group. The prepared Sin-SLN had uniform particle size and high stability. Through joint injection administration, a drug reservoir was formed. Sin-SLN effectively alleviate joint swelling and cartilage damage of rabbit, down-regulated the expression of inflammatory cytokines, and inhibited the epithelial proliferation and inflammatory cell infiltration of the synovial tissue, demonstrating the efficacy in treating RA.


Asunto(s)
Artritis Experimental , Artritis Reumatoide , Animales , Conejos , Factor de Necrosis Tumoral alfa , Fluorescencia , Artritis Reumatoide/tratamiento farmacológico , Interleucina-1 , Artritis Experimental/tratamiento farmacológico
13.
Zhongguo Zhong Yao Za Zhi ; 48(18): 4874-4883, 2023 Sep.
Artículo en Zh | MEDLINE | ID: mdl-37802829

RESUMEN

Rheumatoid arthritis(RA) is a widely prevalent autoimmune inflammatory disease that severely affects patients' quality of life. Currently, conventional formulations against RA have several limitations, such as nonspecificity, poor efficacy, large drug dosages, frequent administration, and systemic side effects. Nanotechnology-based drug delivery systems have emerged as a promising stra-tegy for the diagnosis and treatment of RA since nanotechnology can overcome the limitations of traditional treatments and simplify the complexity of the disease. These systems enable targeted delivery of anti-inflammatory drugs to the inflamed areas through active and passive targeting, achieving specificity to the joints, overcoming the need for increased dosage and administration frequency, and reducing associated adverse reactions. This article aimed to review nanocarrier-based drug delivery systems in the field of RA and elucidate how nanosystems can be utilized to deliver therapeutic drugs to inflamed joints for controlling RA progression. By discussing the current issues and challenges faced by nanodrug delivery systems and highlighting the urgent need for solutions, this article offers theoretical support for further research on nanotechnology-based co-delivery systems in the future.


Asunto(s)
Artritis Reumatoide , Enfermedades Autoinmunes , Humanos , Calidad de Vida , Sistemas de Liberación de Medicamentos , Artritis Reumatoide/tratamiento farmacológico , Enfermedades Autoinmunes/tratamiento farmacológico , Nanotecnología
14.
Angew Chem Int Ed Engl ; 62(30): e202303877, 2023 07 24.
Artículo en Inglés | MEDLINE | ID: mdl-37231526

RESUMEN

A conductive polymer-based photosynthetic biohybrid is constructed to enhance biological nitrogen fixation by increasing nitrogenase activity in the non-photosynthetic bacterium Azotobacter Chroococcum (A. Chroococcum). The light-harvesting cationic poly(fluorene-alt-phenylene) (PFP) electrostatically binds to the surface of the bacteria and possesses satisfactory conductivity to facilitate electron transfer to the bacterium, promoting the nitrogen fixation pathway through redox proteins on the surface of the bacteria when under illumination. Therefore, the nitrogenase activity, hydrogen, NH4 + -N and L-amino acids production are increased by 260 %, 37 %, 44 %, and 47 %, respectively. The expression levels of nifD and nifK encoding molybdenum-iron (MoFe) protein and relevant nitrogen-fixing proteins are up-regulated. These photoactive conductive polymer-bacteria biohybrids provide a new method for improving the biological nitrogen fixation capability of non-photosynthetic nitrogen-fixing bacteria.


Asunto(s)
Fijación del Nitrógeno , Nitrogenasa , Nitrogenasa/metabolismo , Molibdoferredoxina/metabolismo , Hierro/metabolismo , Oxidación-Reducción
15.
Gen Comp Endocrinol ; 325: 114054, 2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-35580689

RESUMEN

The insulin-like androgenic gland hormone gene (IAG) of crustaceans plays pivotal roles in the regulation of sex differentiation. MicroRNAs (miRNAs) are a class of short, non-coding RNAs that function as post-transcriptional gene regulators. However, little information about the regulatory relationship between miRNA and Macrobrachium rosenbergii IAG (MrIAG) were exposed. In this study, we used the 3' untranslated region (UTR) of MrIAG to predict potential target sites of miRNAs. The results showed that miR-184 has one target site in the 3'UTR of MrIAG. Dual-luciferase report assay in vitro confirmed that miR-184 can significantly down-regulate MrIAG expression. Besides, we constructed mutant plasmids of 3'UTR of MrIAG. The result displayed that after co-transfection of mutant plasmids and miR-184 agomir, the activity of luciferase was not affected compared to the control. These results indicated that miR-184 could directly regulate MrIAG. In addition, we found that overexpression of miR-184 in M. rosenbergii can lead to significant changes in the transcription level of genes. Compared with control group, we identified 1510 differentially expressed genes (DEGs) in the miR-184 injection group. Some DEGs were involved in sex differentiation, gonad development, growth and molting were found. qRT-PCR verification was performed on eight DEGs randomly, and the results showed that the expression level of sex-, growth-, and metabolism-related genes changed significantly after MrIAG gene knockdown. Collectively, findings from this study suggest that miR-184, by mediating IAG expression, may be involved in many physiological processes in M. rosenbergii. The current study lays a basic understanding for short-term silencing of MrIAG with miR-184, and facilitates miRNA function analysis in M. rosenbergii in future.


Asunto(s)
MicroARNs , Palaemonidae , Regiones no Traducidas 3' , Andrógenos/metabolismo , Animales , Agua Dulce , Perfilación de la Expresión Génica , Técnicas de Silenciamiento del Gen , Larva/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Palaemonidae/genética , Palaemonidae/metabolismo , Transcriptoma
16.
Zhongguo Zhong Yao Za Zhi ; 47(18): 5008-5021, 2022 Sep.
Artículo en Zh | MEDLINE | ID: mdl-36164911

RESUMEN

The present study explored the main active ingredients and the underlying mechanism of Linderae Radix the treatment of gastric cancer by network pharmacology, molecular docking, and in vitro cell experiments. TCMSP, OMIM and GeneCards database were used to obtain the active ingredients of Linderae Radix to predict the related targets of both Linderae Radix and gastric cancer. After screening the common potential action targets, the STRING database was used to construct the PPI network for protein interaction of the two common targets. Enrichment analysis of GO and KEGG by DAVID database. Based on STRING and DAVID platform data, Cytoscape software was used to construct an "active ingredient-target" network and an "active ingredient-target-pathway" network. Molecular docking was performed using the AutoDock Vina to predict the binding of the active components to the key action targets, and finally the key targets and pathways were verified in vitro. According to the prediction results, there were 9 active components, 179 related targets of Radix Linderae, 107 common targets of Linderae Radix and gastric cancer, 693 biological processes, 57 cell compositions, and 129 molecular functions involved in the targets, and 161 signaling pathways involved in tumor antigen p53, hypoxia-indu-cible factor 1, etc. Molecular docking results showed that the core component, jimadone, had high binding activity with TP53. Finally, in an in vitro experiment, the screened radix linderae active ingredient gemmadone is used for preliminarily verifying the core targets and pathways of the human gastric cancer cell SGC-7901, The results showed that germacrone could significantly inhibit the proliferation of gastric cancer cells and induce the apoptosis of SGC-7901 by regulating the expression of p53, Bax, Bcl-2 and other key proteins. In summary, Radix Linderae can control the occurrence and development of gastric cancer through multi-components, multi-targets and multi-pathways, which will provide theoretical basis for further clinical discussion on the mechanism of Radix Linderae in treating gastric cancer.


Asunto(s)
Medicamentos Herbarios Chinos , Lindera , Medicina Tradicional China , Farmacología en Red , Neoplasias Gástricas , Antígenos de Neoplasias , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Lindera/química , Simulación del Acoplamiento Molecular , Neoplasias Gástricas/tratamiento farmacológico , Proteína p53 Supresora de Tumor , Proteína X Asociada a bcl-2
17.
Angew Chem Int Ed Engl ; 61(14): e202116457, 2022 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-35064623

RESUMEN

Inside living cells, regulation of catalytic activity of artificial enzymes remains challenging due to issues such as biocompatibility, efficiency, and stability of the catalyst, by which the practical applications of artificial enzymes have been severely hindered. Here, an artificial enzyme, PTT-SGH, with responsiveness to reactive oxygen species (ROS), was obtained by introducing a catalytic histidine residue to pentaerythritol tetra(3-mercaptopropionate) (PTT). The artificial enzyme formed large aggregates in cells via the intracellular ROS-mediated oxidation of thiol groups. The process was significantly facilitated in tumor cells because of the higher ROS concentration in the tumor microenvironment. The catalytic activity of this artificial enzyme was intensively enhanced through deprotonation of cross-linked PTT-SGH, which showed typical esterase activities. Selective fluorescence imaging of tumor cells was achieved using the artificial enzyme to trigger the cleavage of the ester bond of the caged fluorophore inside living cells.


Asunto(s)
Neoplasias , Imagen Óptica , Catálisis , Neoplasias/diagnóstico por imagen , Especies Reactivas de Oxígeno , Compuestos de Sulfhidrilo , Microambiente Tumoral
18.
Angew Chem Int Ed Engl ; 60(21): 11758-11762, 2021 05 17.
Artículo en Inglés | MEDLINE | ID: mdl-33724623

RESUMEN

Extensive recent efforts have been put on the design of high-performance organic near-infrared (NIR) photothermal agents (PTAs), especially over NIR-II bio-window (1000-1350 nm). So far, the development is mainly limited by the rarity of molecules with good NIR-II response. Here, we report organic nanoparticles of intermolecular charge-transfer complexes (CTCs) with easily programmable optical absorption. By employing different common donor and acceptor molecules to form CTC nanoparticles (CT NPs), absorption peaks of CT NPs can be controllably tuned from the NIR-I to NIR-II region. Notably, CT NPs formed with perylene and TCNQ have a considerably red-shifted absorption peak at 1040 nm and achieves a good photothermal conversion efficiency of 42 % under 1064 nm excitation. These nanoparticles were used for antibacterial application with effective activity towards both Gram-negative and Gram-positive bacteria. This work opens a new avenue into the development of efficient PTAs.


Asunto(s)
Antibacterianos/farmacología , Nanopartículas/química , Antibacterianos/química , Antibacterianos/efectos de la radiación , Derivados del Benceno/química , Derivados del Benceno/farmacología , Derivados del Benceno/efectos de la radiación , Escherichia coli/efectos de los fármacos , Rayos Infrarrojos , Pruebas de Sensibilidad Microbiana , Nanopartículas/efectos de la radiación , Nitrilos/química , Nitrilos/farmacología , Nitrilos/efectos de la radiación , Perileno/química , Perileno/farmacología , Perileno/efectos de la radiación , Compuestos Policíclicos/química , Compuestos Policíclicos/farmacología , Compuestos Policíclicos/efectos de la radiación , Solubilidad , Staphylococcus aureus/efectos de los fármacos , Electricidad Estática/efectos adversos , Compuestos de Sulfhidrilo/química , Compuestos de Sulfhidrilo/farmacología , Compuestos de Sulfhidrilo/efectos de la radiación , Agua/química
19.
Angew Chem Int Ed Engl ; 60(22): 12424-12430, 2021 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-33760356

RESUMEN

Silkworm silk is a promising natural biopolymer for textile and biomedical applications for its remarkable flexibility, excellent biocompatibility and controllable biodegradability. The functionalization of silks makes them more versatile for flexible displays and visible bioscaffolds. However, fluorescent silks are normally fabricated through unstable physical absorption or complicated chemical reactions under harsh conditions. Herein, we developed a simple strategy for preparing fluorescent silks. Five aggregation-induced emission luminogens (AIEgens) with activated alkynes were synthesized by rational molecular design, and then reacted with silk fibers through facile metal-free click bioconjugation. The resulting conjugates show bright full-color emissions and high stability. A white light-emitting silk was fabricated by simultaneous bioconjugation with red-, green- and blue-emissive AIEgens. The red-emissive AIEgen-functionalized silks were successfully applied for long-term cell tracking and two-photon bioimaging, demonstrating great potential for tissue engineering and bioscaffold monitoring.


Asunto(s)
Materiales Biocompatibles/química , Sustancias Luminiscentes/química , Imagen Óptica/métodos , Seda/química , Células A549 , Alquinos/química , Animales , Bombyx/metabolismo , Química Clic , Humanos , Microscopía de Fluorescencia por Excitación Multifotónica , Puntos Cuánticos/química , Ingeniería de Tejidos
20.
Angew Chem Int Ed Engl ; 58(31): 10660-10665, 2019 07 29.
Artículo en Inglés | MEDLINE | ID: mdl-31173456

RESUMEN

Photodynamic therapy (PDT) is a promising method for cancer treatment. Two parameters that influence the efficacy of PDT are the light source and oxygen supply. Herein, we prepared a system for PDT using hemoglobin (Hb)-linked conjugated polymer nanoparticles (CPNs), which can luminesce and supply oxygen. Hb catalyzes the activation of luminol, the conjugated polymer poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) nanoparticles can absorb the chemiluminescence of luminol through chemiluminescence resonance energy transfer (CRET) and then sensitize the oxygen supplied by Hb to produce reactive oxygen species that kill cancer cells. This system could be used for the controlled release of an anticancer prodrug. The system does not need an external light source and circumvents the insufficient level molecular oxygen under hypoxia. This work provides a proof-of-concept to explore smart and multifunctional nanoplatforms for phototherapy.


Asunto(s)
Antineoplásicos/farmacología , Hemoglobinas/química , Nanopartículas/química , Oxígeno/química , Fármacos Fotosensibilizantes/farmacología , Polímeros/química , Profármacos/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Transferencia Resonante de Energía de Fluorescencia , Células HeLa , Hemoglobinas/metabolismo , Humanos , Luminiscencia , Mediciones Luminiscentes , Imagen Óptica , Fármacos Fotosensibilizantes/química , Fototerapia , Profármacos/química , Especies Reactivas de Oxígeno/metabolismo
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