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1.
J Nanobiotechnology ; 22(1): 98, 2024 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-38461231

RESUMEN

Chemodynamic therapy (CDT) based on intracellular Fenton reaction to produce highly cytotoxic reactive oxygen species (ROS) has played an essential role in tumor therapy. However, this therapy still needs to be improved by weakly acidic pH and over-expression of glutathione (GSH) in tumor microenvironment (TEM), which hinders its future application. Herein, we reported a multifunctional bimetallic composite nanoparticle MnO2@GA-Fe@CAI based on a metal polyphenol network (MPN) structure, which could reduce intracellular pH and endogenous GSH by remodeling tumor microenvironment to improve Fenton activity. MnO2 nanoparticles were prepared first and MnO2@GA-Fe nanoparticles with Fe3+ as central ion and gallic acid (GA) as surface ligands were prepared by the chelation reaction. Then, carbonic anhydrase inhibitor (CAI) was coupled with GA to form MnO2@GA-Fe@CAI. The properties of the bimetallic composite nanoparticles were studied, and the results showed that CAI could reduce intracellular pH. At the same time, MnO2 could deplete intracellular GSH and produce Mn2+ via redox reactions, which re-established the TME with low pH and GSH. In addition, GA reduced Fe3+ to Fe2+. Mn2+ and Fe2+ catalyzed the endogenous H2O2 to produce high-lever ROS to kill tumor cells. Compared with MnO2, MnO2@GA-Fe@CAI could reduce the tumor weight and volume for the xenograft MDA-MB-231 tumor-bearing mice and the final tumor inhibition rate of 58.09 ± 5.77%, showing the improved therapeutic effect as well as the biological safety. Therefore, this study achieved the high-efficiency CDT effect catalyzed by bimetallic through reshaping the tumor microenvironment.


Asunto(s)
Nanopartículas , Neoplasias , Neoplasias de la Mama Triple Negativas , Humanos , Animales , Ratones , Peróxido de Hidrógeno , Compuestos de Manganeso/farmacología , Especies Reactivas de Oxígeno , Óxidos , Ácido Gálico , Glutatión , Concentración de Iones de Hidrógeno , Línea Celular Tumoral , Microambiente Tumoral
2.
ACS Appl Mater Interfaces ; 15(33): 39847-39863, 2023 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-37578471

RESUMEN

The wet environment of water or tissue in bleeding wounds poses significant challenges to the adhesion performance of existing hemostatic adhesives. An intelligent composite adhesive prepared by doping starch-based silicate micro-nanograded porous particles (MBC@CMS) with dopamine-hyperbranched polymers (HPD, 7800 Mw) synthesized by the Michael addition reaction could be triggered by water to form a glue (MBC@CMS-HPD). The results indicated that MBC@CMS-HPD could still have adhesion properties under running water washing and water immersion and could effectively seal the water outlet. The results of the glue-forming mechanism showed that MBC@CMS-HPD had better wettability than water, which could eliminate water molecules at the wet adhesive surface. When contacted with water, the agglomeration of the HPD hydrophobic chain increases the exposure of the catechol group, and the relative atomic mass of the N element on the surface increases from 2.8 to 4.8%. The adhesion of MBC@CMS-HPD was enhanced and stable. MBC@CMS-HPD showed significant hemostasis effects in five injury bleeding models of Sprague-Dawley (SD) rats and New Zealand rabbits. Especially in the fatal femoral artery bleeding model of New Zealand rabbits, MBC@CMS-HPD reduced the amount of bleeding by 75% and shortened the bleeding time by 78% compared with the a-cyanoacrylate adhesives. The results of the coagulation mechanism showed that compared with HPD, MBC@CMS-HPD could activate both endogenous and exogenous coagulation pathways. Among them, after contact with blood, HPD formed a gel to close the blood outlet, and MBC@CMS entered the wound to activate the internal and external coagulation pathways. In addition, HPD and MBC@CMS had good histocompatibility and degradability, which has the potential to be applied to different wounds.


Asunto(s)
Hemostáticos , Adhesivos Tisulares , Ratas , Animales , Conejos , Hemostáticos/farmacología , Hemostáticos/química , Adhesivos/farmacología , Dopamina/farmacología , Dopamina/química , Porosidad , Agua/química , Ratas Sprague-Dawley , Hemostasis , Hemorragia/terapia , Adhesivos Tisulares/química
3.
ACS Biomater Sci Eng ; 9(5): 2470-2482, 2023 05 08.
Artículo en Inglés | MEDLINE | ID: mdl-37084356

RESUMEN

In daily life and during surgery, the skin, as the outermost organ of the human body, is easily damaged to form wounds. If the wound was infected by the bacteria, especially the drug-resistant bacteria such as methicillin-resistant staphylococcus aureus (MRSA), it was difficult to recover. Therefore, it was important to develop the safe antimicrobial strategy to inhibit bacterial growth in the wound site, in particular, to overcome the problem of bacterial drug resistance. Here, the Ag/AgBr-loaded mesoporous bioactive glass (Ag/AgBr-MBG) was prepared, which had excellent photocatalytic properties under simulated daylight for rapid antibacterial activity within 15 min by generating reactive oxygen species (ROS). Meanwhile, the killing rate of Ag/AgBr-MBG against MRSA was 99.19% within 15 min, which further reduced the generation of drug-resistant bacteria. In addition, Ag/AgBr-MBG particles could disrupt bacterial cell membranes, showing the broad-spectrum antibacterial properties and promoting tissue regeneration and infected wound healing. Ag/AgBr-MBG particles might have potential applications as a light-driven antimicrobial agent in the field of biomaterials.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Humanos , Cicatrización de Heridas , Antibacterianos/farmacología , Vidrio , Plata/farmacología
4.
J Mater Chem B ; 11(13): 2830-2851, 2023 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-36916631

RESUMEN

The number of patients with non-healing wounds is generally increasing globally, placing a huge social and economic burden on every country. The complexity of the wound-healing process remains a major health challenge despite the numerous studies that have been reported on conventional wound dressings. Therefore, a therapeutic system that combines diagnostic and therapeutic modalities is essential to monitor wound-related biomarkers and facilitate wound healing in real time. Microneedles, as a multifunctional platform, are promising for transdermal diagnostics and drug delivery. Their advantages are mainly reflected in painless transdermal drug delivery, good biocompatibility, and ease of self-administration. In this work, we review recent advances in the use of microneedle patches for wound healing and monitoring. The paper first provides a brief overview of the skin structure and the wound healing process, and then discusses the current state of research and prospects for the development of wound-related biomarkers and their real-time monitoring based on microneedle sensors. It summarizes the current state of research based on the unique design of microneedle patches, including biomimetic, conductive, and environmentally responsive, to achieve wound healing. It further summarizes the prospects for the application of different microneedle-based drug delivery modalities and drug delivery substances for wound healing, due to their superior transdermal drug delivery advantages. It concludes with challenges and expectations for the use of smart microneedle patches for wound healing and management.


Asunto(s)
Piel , Cicatrización de Heridas , Humanos , Administración Cutánea , Agujas , Sistemas de Liberación de Medicamentos
5.
Mol Med Rep ; 27(2)2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36601740

RESUMEN

Tubulointerstitial fibrosis (TIF) is an important pathological change that occurs during the development of diabetic kidney disease. The epithelial­mesenchymal transition (EMT) of renal tubular epithelial cells is a manifestation of TIF. STAT1, a member of the STAT family of transcription factors, can be modified by the small ubiquitin­related modifier (SUMO), thus affecting the activity of STAT1. The present study investigated the role of STAT1 SUMOylation in high glucose­induced tubular EMT by western blotting, immunocytochemistry, immunofluorescence, co­immunoprecipitation and dual luciferase reporter analysis. The results indicated that in the process of high glucose­induced EMT, STAT1 activation protected the cells from EMT. However, high glucose also increased the SUMOylation of STAT1, which prevented STAT1 from exerting an effective protective role by inhibiting its activity.


Asunto(s)
Transición Epitelial-Mesenquimal , Sumoilación , Humanos , Células Epiteliales/metabolismo , Factores de Transcripción , Glucosa/farmacología , Fibrosis , Factor de Transcripción STAT1/metabolismo
6.
Int J Biol Macromol ; 232: 123271, 2023 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-36646352

RESUMEN

The most important function of skin is to prevent biological dehydration and protect internal structures from the environment. When a wound becomes infected, the bacteria cause a sustained inflammatory response at the infected site, further delaying the healing process. Therefore, the search for better antibacterial strategies has become a topic of great concern. Therefore, the development of multifunctional hydrogels with antibacterial properties, ROS removal, and hemostasis is urgently required for promoting wound healing process. Chitosan is the only cationic natural polysaccharide with good biocompatibility, antibacterial and hemostatic ability. It is a candidate material to prepare hydrogel wound dressing. Hyaluronic acid (HA) is a natural biological macromolecule that belongs to a group of heteropolysaccharides known as non-sulfated glycosaminoglycans. It is a major component of the skin extracellular matrix (ECM) and is involved in inflammation, angiogenesis, and tissue regeneration. Here, the hydrogel was designed with the natural macromolecular of the gallic acid-grafted quaternized chitosan (GA-QCS) and oxidized hyaluronic acid (OHA) via Schiff base and/or Michael addition reaction. It was found that the GA-QCS/OHA hydrogel exhibited multifunctional capabilities with injectable, hemostasis, degradation, and release of medicines. In addiation, GA-QCS/OHA hydrogels exhibited remarkable antioxidant and migration promoting effects in vitro. And the mupirocin-loaded GA-QCS/OHA hydrogels had inhibitory effects on E. coli (Gram-negative bacterium) and S. aureus (Gram-positive bacterium) in vitro. A full-thickness skin of S. aureus infection mouse wound model was used to test the bioactive effect of the hydrogels and the accelerated wound healing was obtained due to the inhibiting the proinflammatory factor TNF-α and upregulating the vascularization factor CD31. This study proposed an effective strategy based on antioxidant, antibacterial, self-healing multifunctional hydrogel for wound healing under various infectious complications. This natural macromolecular hydrogel could act as an effective reactive oxygen species scavenger to promote the wound healing in the future.


Asunto(s)
Quitosano , Ratones , Animales , Quitosano/farmacología , Quitosano/química , Hidrogeles/farmacología , Hidrogeles/química , Antioxidantes/química , Ácido Hialurónico/farmacología , Ácido Hialurónico/química , Staphylococcus aureus , Escherichia coli , Cicatrización de Heridas , Antibacterianos/farmacología , Antibacterianos/química
7.
Int J Mol Sci ; 23(24)2022 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-36555485

RESUMEN

Hypoxia is a major stressor and a prominent feature of pathological conditions, such as bacterial infections, inflammation, wounds, and cardiovascular defects. In this study, we investigated whether reoxygenation has a protective effect against hypoxia-induced acute injury and burn using the C57BL/6 mouse model. C57BL/6 mice were exposed to hypoxia and treated with both acute and burn injuries and were in hypoxia until wound healing. Next, C57BL/6 mice were exposed to hypoxia for three days and then transferred to normoxic conditions for reoxygenation until wound healing. Finally, skin wound tissue was collected to analyze healing-related markers, such as inflammation, vascularization, and collagen. Hypoxia significantly increased inflammatory cell infiltration and decreased vascular and collagen production, and reoxygenation notably attenuated hypoxia-induced infiltration of inflammatory cells, upregulation of pro-inflammatory cytokine levels (IL-6 and TNF-α) in the wound, and remission of inflammation in the wound. Immunofluorescence analysis showed that reoxygenation increased the expression of the angiogenic factor α-SMA and decreased ROS expression in burn tissues compared to hypoxia-treated animals. Moreover, further analysis by qPCR showed that reoxygenation could alleviate the expression of hypoxic-induced inflammatory markers (IL-6 and TNF), increase angiogenesis (SMA) and collagen synthesis (Col I), and thus promote wound healing. It is suggested that oxygen can be further evaluated in combination with oxygen-releasing materials as a supplementary therapy for patients with chronic hypoxic wounds.


Asunto(s)
Quemaduras , Interleucina-6 , Ratones , Animales , Ratones Endogámicos C57BL , Cicatrización de Heridas , Hipoxia/complicaciones , Colágeno , Oxígeno/farmacología , Quemaduras/patología , Inflamación/metabolismo
8.
Acta Biomater ; 154: 231-243, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36210045

RESUMEN

Hypoxic nonhealing wounds are a common complication in chronic patients, and chronic hypoxia is the main reason for delayed wound healing, so local wound oxygenation may be an effective way to address this problem. Here, we proposed a system consisting of oxygen-releasing microsphere (GC) and self-healing hydrogel (QGO). QGO/GC hydrogel could promote survival, migration and tube formation of human umbilical vein endothelial cells under hypoxic conditions. Moreover, QGO/GC hydrogels exhibited biocompatibility in vitro and in vivo. The hypoxic mouse burn model further confirmed that QGO/GC hydrogel could promote tissue repair by reducing inflammation (TNF-α and IL-1ß), increasing angiogenesis (CD31, VEGF and α-SMA) and collagen deposition. This study provided an effective oxygen-releasing hydrogel that could offer a simple and effective method for the clinical treatment of chronic hypoxic wounds. STATEMENT OF SIGNIFICANCE: Burn injury is caused by various exogenous factors such as friction, cold, radiations, electricity, chemicals, hot surfaces or liquids. Severe burn can damage the entire skin layer, and the healing process is delayed due to an unbalanced inflammatory response, excessive reactive oxygen species, lack of angiogenesis (insufficient nutrient and oxygen availability), and susceptibility to infection. In the present study, we proposed an oxygen-releasing hydrogel (QGO/GC). QGO/GC hydrogel could promote survival, migration, and tube formation of human umbilical vein endothelial cells under hypoxic conditions. And QGO/GC hydrogels could promote tissue repair by reducing inflammation, increasing angiogenesis and collagen deposition. This work provided an effective oxygen-releasing hydrogel for the clinical management of chronic hypoxic wounds.


Asunto(s)
Quemaduras , Hidrogeles , Ratones , Animales , Humanos , Hidrogeles/farmacología , Hidrogeles/uso terapéutico , Oxígeno/farmacología , Quemaduras/tratamiento farmacológico , Células Endoteliales de la Vena Umbilical Humana , Colágeno/farmacología , Modelos Animales de Enfermedad , Hipoxia
9.
Eur J Med Chem ; 244: 114843, 2022 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-36265281

RESUMEN

Cancer seriously endangers human life and health. Recently, the development of AIEgens with aggregation-induced emission (AIE) effect as a new generation of photosensitizers (PSs) to circumvent aggregation-induced fluorescence quenching and reduction of ROS generation has received extensive attention in photodynamic therapy (PDT), a non-invasive anticancer therapy. Rational molecular design can enhance the photosensitization of AIE PSs to achieve effective PDT and can realize the construction of functionalized AIE PSs and synergistic therapy based on AIE PSs. To improve the efficacy of AIE PSs for cancer treatment, many groups have conducted molecular design studies and produced exciting results. This review summarizes the molecular design strategies of three types of AIE PSs for effective photodynamic therapy, focusing on the design strategies of pure organic small molecule type AIE PSs, and reviews the existing design strategies of metal complexes and conjugated polymers. Subsequently, the design strategy to achieve synergistic treatment of AIE PSs from molecular modifications is summarized. The challenges and prospects of the AIE PSs research field are further discussed.


Asunto(s)
Antineoplásicos , Diseño de Fármacos , Fotoquimioterapia , Fármacos Fotosensibilizantes , Humanos , Antineoplásicos/química , Antineoplásicos/farmacología , Fluorescencia , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Especies Reactivas de Oxígeno
10.
Biomolecules ; 12(9)2022 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-36139080

RESUMEN

Diabetes-related chronic wounds are often accompanied by a poor wound-healing environment such as high glucose, recurrent infections, and inflammation, and standard wound treatments are fairly limited in their ability to heal these wounds. Metal-organic frameworks (MOFs) have been developed to improve therapeutic outcomes due to their ease of engineering, surface functionalization, and therapeutic properties. In this review, we summarize the different synthesis methods of MOFs and conduct a comprehensive review of the latest research progress of MOFs in the treatment of diabetes and its wounds. State-of-the-art in vivo oral hypoglycemic strategies and the in vitro diagnosis of diabetes are enumerated and different antimicrobial strategies (including physical contact, oxidative stress, photothermal, and related ions or ligands) and provascular strategies for the treatment of diabetic wounds are compared. It focuses on the connections and differences between different applications of MOFs as well as possible directions for improvement. Finally, the potential toxicity of MOFs is also an issue that we cannot ignore.


Asunto(s)
Antiinfecciosos , Diabetes Mellitus , Estructuras Metalorgánicas , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/terapia , Glucosa , Humanos , Hipoglucemiantes , Iones , Estructuras Metalorgánicas/uso terapéutico
11.
Int J Nanomedicine ; 17: 2611-2628, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35712639

RESUMEN

In recent years, chemodynamic therapy (CDT) has received extensive attention as a novel means of cancer treatment. The CDT agents can exert Fenton and Fenton-like reactions in the acidic tumor microenvironment (TME), converting hydrogen peroxide (H2O2) into highly toxic hydroxyl radicals (·OH). However, the pH of TME, as an essential factor in the Fenton reaction, does not catalyze the reaction effectively, hindering its efficiency, which poses a significant challenge for the future clinical application of CDT. Therefore, this paper reviews various strategies to enhance the antitumor properties of nanomaterials by modulating tumor acidity. Ultimately, the performance of CDT can be further improved by inducing strong oxidative stress to produce sufficient ·OH. In this paper, the various acidification pathways and proton pumps with potential acidification functions are mainly discussed, such as catalytic enzymes, exogenous acids, CAIX, MCT, NHE, NBCn1, etc. The problems, opportunities, and challenges of CDT in the cancer field are also discussed, thereby providing new insights for the design of nanomaterials and laying the foundation for their future clinical applications.


Asunto(s)
Peróxido de Hidrógeno , Neoplasias , Línea Celular Tumoral , Humanos , Peróxido de Hidrógeno/metabolismo , Concentración de Iones de Hidrógeno , Radical Hidroxilo/metabolismo , Neoplasias/terapia , Microambiente Tumoral
12.
Lab Invest ; 102(9): 966-978, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35523949

RESUMEN

Circular RNAs (circRNAs) are regulators of gene expression that can regulate cell proliferation and programmed cell death and serve as biomarkers in renal diseases. However, the specific traits and underlying mechanisms of circRNAs in the progression of lupus nephritis (LN) have not been elucidated. In the present study, we clarified that hsa_circ_0054595 (circRTN4) was upregulated in human renal mesangial cells (HRMCs). In cultured HRMCs, circRTN4 could enhance FN expression by directly interacting with miR-513a-5p. High circRTN4 expression in monocytes disseminated into HRMCs in an exosomal manner, thereby accelerating cell proliferation and extracellular matrix deposition. In addition, knockdown of circRTN4 in the kidney or peripheral blood alleviated renal damage in MRL/lpr and BALB/c mice. Clinically, high levels of circRTN4 were found in peripheral blood mononuclear cells and kidney tissues of LN patients, hence serving as an effective biomarker for LN detection and a novel therapeutic target. Our findings indicated that circRTN4 exacerbates mesangial cell dysfunction by activating the miR-513a-5p/FN axis in lupus nephritis.


Asunto(s)
Nefritis Lúpica , MicroARNs , Animales , Proliferación Celular , Fibronectinas , Humanos , Leucocitos Mononucleares , Células Mesangiales , Ratones , Ratones Endogámicos MRL lpr , ARN Circular
14.
Artículo en Inglés | MEDLINE | ID: mdl-33789908

RESUMEN

INTRODUCTION: Although various lipid and non-lipid analytes measured by nuclear magnetic resonance (NMR) spectroscopy have been associated with type 2 diabetes, a structured comparison of the ability of NMR-derived biomarkers and standard lipids to predict individual diabetes risk has not been undertaken in larger studies nor among individuals at high risk of diabetes. RESEARCH DESIGN AND METHODS: Cumulative discriminative utilities of various groups of biomarkers including NMR lipoproteins, related non-lipid biomarkers, standard lipids, and demographic and glycemic traits were compared for short-term (3.2 years) and long-term (15 years) diabetes development in the Diabetes Prevention Program, a multiethnic, placebo-controlled, randomized controlled trial of individuals with pre-diabetes in the USA (N=2590). Logistic regression, Cox proportional hazards model and six different hyperparameter-tuned machine learning algorithms were compared. The Matthews Correlation Coefficient (MCC) was used as the primary measure of discriminative utility. RESULTS: Models with baseline NMR analytes and their changes did not improve the discriminative utility of simpler models including standard lipids or demographic and glycemic traits. Across all algorithms, models with baseline 2-hour glucose performed the best (max MCC=0.36). Sophisticated machine learning algorithms performed similarly to logistic regression in this study. CONCLUSIONS: NMR lipoproteins and related non-lipid biomarkers were associated but did not augment discrimination of diabetes risk beyond traditional diabetes risk factors except for 2-hour glucose. Machine learning algorithms provided no meaningful improvement for discrimination compared with logistic regression, which suggests a lack of influential latent interactions among the analytes assessed in this study. TRIAL REGISTRATION NUMBER: Diabetes Prevention Program: NCT00004992; Diabetes Prevention Program Outcomes Study: NCT00038727.


Asunto(s)
Diabetes Mellitus Tipo 2 , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/prevención & control , Humanos , Lípidos , Lipoproteínas , Aprendizaje Automático , Factores de Riesgo
15.
Lab Invest ; 101(8): 983-997, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33854173

RESUMEN

Tripartite motif-containing 27 (TRIM27) belongs to the triple motif (TRIM) protein family, which plays a role in a variety of biological activities. Our previous study showed that the TRIM27 protein was highly expressed in the glomerular endothelial cells of patients suffering from lupus nephritis (LN). However, whether TRIM27 is involved in the injury of glomerular endothelial cells in lupus nephritis remains to be clarified. Here, we detected the expression of the TRIM27 protein in glomerular endothelial cells in vivo and in vitro. In addition, the influence of TRIM27 knockdown on endothelial cell damage in MRL/lpr mice and cultured human renal glomerular endothelial cells (HRGECs) was explored. The results revealed that the expression of TRIM27 in endothelial cells was significantly enhanced in vivo and in vitro. Downregulating the expression of TRIM27 inhibited the breakdown of the glycocalyx and the injury of endothelial cells via the FoxO1 pathway. Moreover, HRGECs transfected with the WT-FoxO1 plasmid showed a reduction in impairment caused by LN plasma. Furthermore, suppression of the protein kinase B (Akt) pathway could attenuate damage by mediating the expression of TRIM27. Thus, the present study showed that TRIM27 participated in the injury of glomerular endothelial cells and served as a potential therapeutic target for the treatment of lupus nephritis.


Asunto(s)
Proteínas de Unión al ADN , Proteína Forkhead Box O1 , Glomérulos Renales/metabolismo , Nefritis Lúpica/metabolismo , Proteínas Nucleares , Animales , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Células Endoteliales/citología , Femenino , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Humanos , Glomérulos Renales/citología , Glomérulos Renales/patología , Nefritis Lúpica/patología , Ratones , Ratones Endogámicos MRL lpr , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Transducción de Señal/genética , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo
16.
Int J Hyg Environ Health ; 232: 113680, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33348273

RESUMEN

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are widely used chemicals, some of which have been linked to type 2 diabetes. We tested whether PFAS concentrations were cross-sectionally associated with metabolites previously shown to predict incident type 2 diabetes using the Diabetes Prevention Program (DPP), a trial of individuals at high risk of type 2 diabetes. METHODS: We evaluated 691 participants enrolled in the DPP with baseline measures of 10 PFAS (including total perfluorooctanesulfonic acid (PFOS), total perfluorooctanoic acid (PFOA), and Sb-PFOA [branched isomers of PFOA]) and 77 metabolites. We used log2-transformed PFAS concentrations as exposures and standardized metabolite concentrations as outcomes in linear regression models adjusted for age, sex, race/ethnicity, use of anti-hyperlipidemic or triglyceride-lowering medication, income, years of education, marital status, smoking, and family history of diabetes, with Benjamini-Hochberg linear step-up false discovery rate correction. RESULTS: Sb-PFOA was associated with the largest number of tested metabolites (29 of 77). Each doubling in Sb-PFOA was associated with higher leucine (ß = 0.07 [95%CI: 0.02, 0.11] SD) and lower glycine (-0.08 [95%CI: 0.03, -0.13] SD). Each doubling of either total PFOA or n-PFOA was associated with -0.13 [95%CI: 0.04, -0.22] SD lower glycine. PFOA and Sb-PFOA were positively associated with multiple triacylglycerols and diacylglycerols, and total PFOS, total PFOA, and Sb-PFOA were positively associated with phosphatidylethanolamines. CONCLUSIONS: PFAS concentrations are associated with metabolites linked to type 2 diabetes (particularly amino acid, glycerolipid and glycerophospholipid pathways). Further prospective research is needed to test whether these metabolites mediate associations of PFAS and type 2 diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2 , Contaminantes Ambientales , Biomarcadores , Diabetes Mellitus Tipo 2/prevención & control , Humanos , Metabolómica , Proyectos de Investigación
17.
Int J Nanomedicine ; 15: 10285-10304, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33376322

RESUMEN

BACKGROUND: Combined chemotherapy is often affected by the different physicochemical properties of chemotherapeutic drugs, which should be improved by the reasonable design of co-loaded preparations. PURPOSE: A kind of simple but practical graphene oxide (GO) wrapped mesoporous silica nanoparticles (MSN) modified with hyaluronic acid (MSN@GO-HA) were developed for the co-delivery of cinnamaldehyde (CA) and doxorubicin (DOX), in order to enhance their combined treatment on tumor cells and reduce their application defects. METHODS: The MSNCA@GODOX-HA was constructed by MSNCA (loading CA via physical diffusion) and GODOX-HA (modified with HA and loading DOX via π-π stacking) through the electrostatic adsorption, followed by the physicochemical characterization, serum stability and in vitro release study. Cytotoxicity on different cells was detected, followed by the tumor cell uptake tests. The intracellular reactive oxygen species (ROS) changes, mitochondrial functions and activities of caspase-3/-9 in MCF-7 cells were also evaluated, respectively. RESULTS: The MSNCA@GODOX-HA nanoparticles kept stable in FBS solution and achieved pH-responsive release behavior, which was beneficial to increase the accumulation of CA and DOX in tumor cells to enhance the treatment. MSNCA@GODOX-HA exerted higher cytotoxicity to MCF-7 human breast cancer cells than H9c2 cardiac myocyte cells, which were not only attributed to the active targeting to tumor cells by HA, but also related with the activation of intrinsic apoptotic pathway in MCF-7 cells induced by CA, which was mediated by the specific ROS signal amplification and the interference with mitochondrial function. Moreover, the efficacy of DOX was also enhanced by the above process. CONCLUSION: The establishment of the MSNCA@GODOX-HA nanoparticles played a role in promoting strengths and restricting shortcomings of CA and DOX, thereby exerting their function and achieving efficient treatment against cancer.


Asunto(s)
Acroleína/análogos & derivados , Apoptosis/efectos de los fármacos , Doxorrubicina/farmacología , Portadores de Fármacos/química , Grafito/química , Nanopartículas/química , Dióxido de Silicio/química , Acroleína/química , Acroleína/farmacología , Doxorrubicina/química , Humanos , Células MCF-7 , Porosidad , Especies Reactivas de Oxígeno/metabolismo
18.
Fitoterapia ; 147: 104766, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33130231

RESUMEN

Two new compounds, triacremoniate (1) and dietziamide C (2) along with known compounds ß-Adenosine (3) and acrepyrone A (4) were obtained from the mangrove-derived fungus Acremonium citrinum. MMF4. Their structures were unambiguously determined by extensive spectroscopic methods, including UV, IR, HRESIMS and NMR. Triacremoniate (1) can promote apoptosis of HeLa cells by increasing the PARP cleavage and the phosphorylation of JNK and p38.


Asunto(s)
Acremonium/química , Antineoplásicos/farmacología , Productos Biológicos/farmacología , Antineoplásicos/aislamiento & purificación , Productos Biológicos/aislamiento & purificación , China , Células HeLa , Humanos , Estructura Molecular , Raíces de Plantas/microbiología , Rhizophoraceae/microbiología
19.
Materials (Basel) ; 13(14)2020 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-32668643

RESUMEN

In this work, we study the behavior of a composite rod consisting of a piezoelectric semiconductor layer and two piezomagnetic layers under an applied axial magnetic field. Based on the phenomenological theories of piezoelectric semiconductors and piezomagnetics, a one-dimensional model is developed from which an analytical solution is obtained. The explicit expressions of the coupled fields and the numerical results show that an axially applied magnetic field produces extensional deformation through piezomagnetic coupling, the extension then produces polarization through piezoelectric coupling, and the polarization then causes the redistribution of mobile charges. Thus, the composite rod exhibits a coupling between the applied magnetic field and carrier distribution through combined piezomagnetic and piezoelectric effects. The results have potential applications in piezotronics when magnetic fields are relevant.

20.
Ultrasonics ; 108: 106176, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32504985

RESUMEN

Propagation characteristics of Lamb waves in a bilayer plate comprised of a PMN-PT single crystal layer and an elastic layer were investigated in this study. The profiles of the bilayer plate's upper and lower surfaces and the common interface between the PMN-PT and elastic layers were assumed to be periodic corrugation instead of perfect planes. The PMN-PT single crystal was poled along the [0 1 1]c direction with macroscopic symmetry of orthonormal mm2. The dispersion relations of Lamb waves for electrically open and electrically short boundary conditions were derived in the closed form. The effects of the related corrugation parameters and thickness ratios of the PMN-PT single crystal layer to the elastic layer on the phase velocity were assessed using the numerical results. The parameters of the amplitudes and wavenumbers related to the periodic corrugation played key roles in the propagation and dispersion behaviors of the Lamb waves. The phase velocity increased, especially in a lower wavenumber range when the upper or lower surfaces were considered corrugated contours. However, the phase velocity decreased when the common interface was treated as a corrugated configuration. The smaller thickness ratio produced higher phase velocity. These results can provide some fundamental characteristics for the design and application of acoustic wave devices fabricated with PMN-PT single crystals, especially for improving the efficiency and sensitivity.

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