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1.
Mol Biol Rep ; 50(2): 1079-1087, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36385666

RESUMEN

BACKGROUND: Our previous studies showed that Shikonin (SK) had a strong anti-Candida albican (C. albicans) activity, especially against some fluconazole-resistant strains, which is probably due to the oxidative damage of SK to C. albicans. METHODS AND RESULTS: In this study, we expanded the antifungal spectrum and evaluate the toxicity of SK. The results indicated that SK also exhibited potent invitro antifungal activities against other pathogenic fungi such as other Candida, Aspergillus, Cryptococcus, and Dermatophytes, but did not display apparent toxicity to the mammalian cells, suggesting that SK is safe to be a potential antifungal drug. Furtherly, we analyze the exact mechanism of SK against C. albicans. We found that SK could induce a series of apoptosis characteristics, including phosphatidylserine externalization, chromatin condensation and fragmentation, decreased cytochrome c oxidase activity as well as caspase activation. CONCLUSIONS: In summary, this study highlighted the antifungal activity and mechanism of SK against C. albicans, providing a potential therapeutic strategy for C. albicans infection.


Asunto(s)
Antifúngicos , Candida albicans , Animales , Humanos , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Pruebas de Sensibilidad Microbiana , Apoptosis , Candida , Necrosis , Mamíferos
2.
Nutr Metab Cardiovasc Dis ; 33(9): 1716-1724, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37414667

RESUMEN

BACKGROUND AND AIM: Estimated pulse wave velocity (ePWV) measurements have good agreement with PWV measurements. However, the relationship between ePWV and the risk of new-onset diabetes remains unclear. Therefore, this study aimed to investigate whether ePWV was associated with new-onset diabetes. METHODS AND RESULTS: Based on a secondary analysis of the Chinese Rich Health Care Group's cohort study, 211,809 participants who met the criteria were enrolled and divided into four groups based on the ePWV quartiles. Diabetes events are of interest as a result of the study. Over a mean follow-up of 3.12 years, 3000 male (1.41%) and 1173 female (0.55%) patients were diagnosed with new-onset diabetes. The cumulative incidence curves based on quartile subgroups showed that the Q4 group had a significantly higher overall incidence of diabetes than the other subgroups. A multivariate Cox regression analysis showed that ePWV was an independent predictor of new-onset diabetes (hazard ratio, 1.233; 95% confidence interval, 1.198-1.269; P < 0.001). The receiver operating characteristic curve showed that the predictive value was higher than for age and blood pressure. The ePWV was treated as a continuous variable using MaxStat, which identified that the best cut-off point for diabetes risk was 8.47 m/s. A stratified analysis showed that the association between ePWV and the risk of diabetes remained significant in multiple strata. CONCLUSIONS: An elevated ePWV was independently associated with an increased risk of developing diabetes in Chinese adults. Thus, ePWV may be a reliable indicator of the risk of early diabetes.


Asunto(s)
Diabetes Mellitus , Rigidez Vascular , Adulto , Humanos , Masculino , Femenino , Estudios de Cohortes , Factores de Riesgo , Análisis de la Onda del Pulso , Tamaño de la Muestra , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología
3.
Lipids Health Dis ; 22(1): 206, 2023 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-38017484

RESUMEN

BACKGROUND AND OBJECTIVE: Although the the Dietary Inflammatory Index (DII) serves to be one of the reliable indicator for hyperlipidaemia, there is still uncertainty about its relationship to prognosis in the hyperlipidaemic population. In current study, the DII levels were analyzed in relation to the mortality risk among among the hyperlipidaemic individuals with the aim of determining any prospective correlation. METHODS: 14,460 subjects with hyperlipidaemia from the 10-year (2001-2010) National Health and Nutrition Examination Survey (NHANES) were chosen for this study. The endpoint event for follow-up was all-cause mortality, and subjects were tracked for up to December 31, 2019, or death, whichever occurred first. The tertiles of the DII levels were utilized for categorizing the study population into three groups. Survival curves, Cox proportional hazards regression models, restricted cubic spline (RCS), subgroup and interaction analyses, and sensitivity analyses were employed sequentially for the purpose of evaluating the association of the DII with mortality. RESULTS: 3170 (21.92%) all-cause deaths were recorded during an average 148-month follow-up period. Kaplan-Meier survival curves indicated that the survival rate of participants divided into the low DII group was substantially improved compared to that of those in the higher DII group (log-rank P < 0.001). After controlling for confounders, higher levels of DII were observed to be meaningfully linked to an elevated risk of death, no matter whether DII was specified for the continuous (hazard ratio (HR): 1.06; 95% confidence interval (CI): 1.04-1.08) or the categorical variable (HR: 1.22; 95% CI: 1.11-1.33). The DII and mortality displayed a linear association, according to the RCS. Stratified and sensitivity analyses reinforced the proof that these findings were reliable. CONCLUSION: Among patients with hyperlipidaemia, the risk of death was positively and linearly linked with DII levels.


Asunto(s)
Enfermedades Cardiovasculares , Hiperlipidemias , Neoplasias , Humanos , Encuestas Nutricionales , Estudios Prospectivos , Enfermedades Cardiovasculares/etiología , Neoplasias/complicaciones , Dieta/efectos adversos , Inflamación/etiología , Hiperlipidemias/complicaciones
4.
Mol Microbiol ; 115(6): 1323-1338, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33400299

RESUMEN

Mitochondria play essential roles in eukaryotic cells for glucose metabolism to produce ATP. In Schizosaccharomyces pombe, transcription factor Rst2 can be activated upon glucose deprivation. However, the link between Rst2 and mitochondrial function remains elusive. Here, we monitored Rst2 transcriptional activity in living cells using a Renilla luciferase reporter system, and found that inhibition of mitochondrial complex III/IV caused cells to produce reactive oxygen species (ROS) and nitric oxide (NO), which in turn activated Rst2. Furthermore, Rst2-GFP was observed to translocate from cytoplasm to nucleus upon mitochondrial complex III/IV inhibitors treatment, and deletion of genes associated with complex III/IV resulted in delayed process of Rst2-GFP nuclear exportation under glucose-rich condition. In particular, we found that Rst2 was phosphorylated following the treatment of complex III/IV inhibitors or SNAP. Altogether, our findings suggest that mitochondrial complex III/IV participates in the activation of Rst2 through ROS and NO generation in Schizosaccharomyces pombe.


Asunto(s)
Complejo III de Transporte de Electrones/metabolismo , Complejo IV de Transporte de Electrones/metabolismo , Óxido Nítrico/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Proteínas de Schizosaccharomyces pombe/metabolismo , Schizosaccharomyces/metabolismo , Factores de Transcripción/metabolismo , Transporte Activo de Núcleo Celular/fisiología , Complejo III de Transporte de Electrones/antagonistas & inhibidores , Complejo III de Transporte de Electrones/genética , Complejo IV de Transporte de Electrones/antagonistas & inhibidores , Complejo IV de Transporte de Electrones/genética , Activación Enzimática/fisiología , Mitocondrias/metabolismo , Fosforilación , S-Nitroso-N-Acetilpenicilamina/farmacología , Schizosaccharomyces/genética , Transcripción Genética/genética
5.
Small ; 18(11): e2107196, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35060331

RESUMEN

Solid photothermal materials with favorable biocompatibility and modifiable mechanical properties demonstrate obvious superiority and growing demand. In this work, polydopamine (PDA) induced functionalization of regenerated silk fibroin (RSF) fibers has satisfactory photothermal conversion ability and flexibility. Based on multilevel engineering, RSF solution containing PDA nanoparticles is wet spun to PDA-incorporating RSF (PDA@RSF) fibers, and then the fibers are coated with PDA via oxidative self-polymerization of dopamine to form PDA@RSF-PDA (PRP) fibers. During the wet spinning process, PDA is to adjust the mechanical properties of RSF by affecting its hierarchical structure. Meanwhile, coated PDA gives the PRP fibers extensive absorption of near-infrared light and sunlight, which is further fabricated into PRP fibrous membranes. The temperature of PRP fibrous membranes can be adjusted and increases to about 50 °C within 360 s under 808 nm laser irradiation with a power density of 0.6 W cm-2 , and PRP fibrous membranes exhibit effective photothermal cytotoxicity both in vitro and in vivo. Under the simulated sunlight, the temperature of PRP fiber increases to more than 200 °C from room temperature and the material can generate 4.5 V voltage when assembled with a differential thermal battery, which means that the material also has the potential for flexible wearable electronic devices.


Asunto(s)
Fibroínas , Fibroínas/química , Indoles/química , Polímeros/química , Ingeniería de Tejidos
6.
Pharm Dev Technol ; 27(6): 635-645, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35787731

RESUMEN

Remdesivir is one of the effective drugs proposed for the treatment of coronavirus disease 2019 (COVID-19). However, the study on inhalable regimen is currently limited though COVID-19 is respiratory diseases and infects lung area. This work aims to prepare inhalable remdesivir formulations and verify their effectiveness through in vitro evaluations. Formulations containing different ratios of jet-milled inhalable remdesivir (5, 10, 20,40, and 70%) with excipients were produced and characterized in terms of the particle size distribution, particle morphology, flowability, water content, crystallinity, the water sorption and desorption capabilities, and the aerodynamic performance. Results indicating that drug loading are a vital factor in facilitating the dispersion of remdesivir dry powder, and the ternary excipient plays a negligible role in improving aerosol performance. Besides, the 70% remdesivir with lactose carrier (70% RD-Lac) was physically stable and retain high aerosol performance after conditioned at 40 °C and 75% RH for a month. Therefore, formulation 70% RD-Lac might be recommended as a candidate product for the potential treatment of COVID-19.


Asunto(s)
Tratamiento Farmacológico de COVID-19 , Excipientes , Adenosina Monofosfato/análogos & derivados , Administración por Inhalación , Alanina/análogos & derivados , Inhaladores de Polvo Seco/métodos , Humanos , Lactosa , Tamaño de la Partícula , Polvos , Aerosoles y Gotitas Respiratorias , Agua
7.
Cell Biol Int ; 45(9): 1897-1905, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33945665

RESUMEN

Hepatoblastoma (HB) is the predominant hepatic neoplasm in infants and young children. Sorafenib has been used to treat adult and pediatric hepatocellular carcinoma. However, efficacy of monotherapy of sorafenib in HB is not sustained. In this study, we tested a possible combinatory therapy of sorafenib with the CCAAT/enhancer-binding proteins (C/EBP) overexpression in HB cell line. Firstly, we evaluated the expression level of C/EBPß in the patients with HB by analyzing The Cancer Genome Atlas data. Lower level of C/EBPß was observed in tumor tissues in comparison with matched normal tissues. Next, we observed that combination of sorafenib and C/EBPß overexpression led to dramatic growth and migration inhibition of live tumor cells which implied promising probability for clinical trial. Mechanistically, C/EBPß which can be downregulated by Ras v12, augmented messenger RNA and protein levels of p53. These data suggested that a combination of sorafenib and C/EBPß overexpression inhibited tumor growth synergistically and provided a promising approach to treat HB.


Asunto(s)
Antineoplásicos/farmacología , Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Hepatoblastoma/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Sorafenib/farmacología , Animales , Niño , Femenino , Células Hep G2 , Humanos , Masculino , Ratones , Ratones Desnudos
8.
Artículo en Inglés | MEDLINE | ID: mdl-32571823

RESUMEN

Invasive fungal diseases are a leading cause of mortality among immunocompromised populations. Treatment is notoriously difficult due to the limited number of antifungal drugs as well as the emergence of drug resistance. Tamoxifen (TAM), a selective estrogen receptor modulator frequently used for the treatment of breast cancer, has been found to have antifungal activities and may be a useful addition to the agents used to treat fungal infectious diseases. However, the molecular mechanisms underlying its antifungal actions remain obscure. Here, we screened for mutations that confer sensitivity to azole antifungal drugs by using the fission yeast Schizosaccharomyces pombe as a model and isolated a mutant with a mutation in cls1 (ccr1), an allele of the gene encoding the NADPH-cytochrome P450 reductase Ccr1. We found that strains with a deletion of the ccr1+ gene exhibited hypersensitivities to various drugs, including antifungal drugs (azoles, terbinafine, micafungin), the immunosuppressor FK506, and the anticancer drugs TAM and 5-fluorouracil (5-FU). Unexpectedly, the overexpression of Ccr1 caused yeast cell resistance to TAM but not the other drugs tested here. Additionally, strains with a deletion of Ccr1 displayed pleiotropic phenotypes, including defects in cell wall integrity and vacuole fusion, enhanced calcineurin activity, as well as increased intracellular Ca2+ levels. Overexpression of the constitutively active calcineurin suppressed the drug-sensitive phenotypes of the Δccr1 cells. Notably, TAM treatment of wild-type cells resulted in pleiotropic phenotypes, similar to those of cells lacking Ccr1. Furthermore, TAM inhibited Ccr1 NADPH-cytochrome P450 reductase activities in a dose-dependent manner. Moreover, TAM treatment also inhibited the NADPH-cytochrome P450 reductase activities of Candida albicans and resulted in defective cell wall integrity. Collectively, our findings suggest that Ccr1 is a novel target of TAM and is involved in the antifungal activity of TAM by regulating cell wall integrity in fission yeast.


Asunto(s)
NADPH-Ferrihemoproteína Reductasa , Proteínas de Schizosaccharomyces pombe , Schizosaccharomyces , Antifúngicos/farmacología , Pared Celular , NADPH-Ferrihemoproteína Reductasa/genética , Schizosaccharomyces/enzimología , Schizosaccharomyces/genética , Proteínas de Schizosaccharomyces pombe/genética , Tamoxifeno/farmacología
9.
Biochem Biophys Res Commun ; 531(2): 160-165, 2020 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-32782153

RESUMEN

In the first station of central odor processing, the main olfactory bulb, signal processing is regulated by synaptic interactions between glutamatergic and GABAergic inputs of the mitral cells (MCs), the major projection neurons. Our previous study has found that repetitive postsynaptic spiking within a critical time window after presynaptic activation by natural odorant stimulation results in persistent enhancement of glutamatergic inputs of MCs in larval zebrafish. Here we observed a long-term depression of GABAergic synapses induced by the same protocol. This long-term depression was mediated by presynaptic NMDA receptors (NMDARs). Further dissecting GABAergic neurotransmission revealed that the STDP-induction protocol induced persistent modification in recurrent and lateral inhibition with opposite directions and distinct requirements on NMDARs. Thus, at the plasticity level, different types of GABAergic inhibition may utilize different mechanisms to cooperate or compete with excitatory inputs to optimize patterns of olfactory bulb output.


Asunto(s)
Plasticidad Neuronal/fisiología , Odorantes , Bulbo Olfatorio/fisiología , Sinapsis/fisiología , Pez Cebra/crecimiento & desarrollo , Ácido gamma-Aminobutírico/metabolismo , Potenciales de Acción , Animales , Potenciación a Largo Plazo , Bulbo Olfatorio/citología , Terminales Presinápticos/fisiología , Receptores de N-Metil-D-Aspartato/metabolismo
10.
Inorg Chem ; 57(24): 15526-15536, 2018 Dec 17.
Artículo en Inglés | MEDLINE | ID: mdl-30500167

RESUMEN

We herein reported the syntheses, structures, and magnetic properties of three dinuclear heterometallic MIILnIII complexes, namely, [MIILnIII(H2L)(CH3OH)2(NO3)2](NO3)·S (M = Co, Ln = Dy, S = MeOH (1CoDy); M = Zn, Ln = Dy, S = MeOH (2ZnDy); M = Co, Ln = Y, S = MeNO2 (3CoY), H4L = 2,6-diacetylpyridine bis[2-(semicarbazono) propionylhydrazone]. Synthesized from the predesigned multidentate ligand H4L, which has two different coordination pockets (smaller N3O2 and larger N2O4 pockets) suitable for either a 3d or a 4f metal center, all these complexes have very similar structures, where the MII centers possess a pentagonal bipyramidal (PBP) geometry and the LnIII sites have a tetradecahedron geometry. Magnetic measurements on these compounds revealed the existence of weak ferromagnetic coupling between the Co2+ and Dy3+ centers and the field-induced slow magnetic relaxation of all three complexes. Furthermore, theoretical calculation on all these complexes indicates that although the change of the diamagnetic Zn2+ ion to the paramagnetic Co2+ ion only slightly modifies the local magnetic anisotropy of the Dy3+ ion, the weak Co-Dy magnetic interaction decreases the energy barrier. These compounds are the first systematic results of a heterometallic 3d-4f single-molecule magnet containing predesigned PBP 3d metal ions.

11.
Inorg Chem ; 55(22): 11621-11625, 2016 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-27934315

RESUMEN

A novel high-nuclear nanosized cluster modified by conjugated organic ligands (pyridine and imidazole), [C5NH5]8[C3H5N2]2{[C5NH5]9[H31Mo12O24Co12(PO4)23(H2O)4]}·12H2O (1), has been successfully isolated under hydrothermal conditions and structurally characterized. Compound 1 consists of 12 CoII and 12 MoV ions linked by 23 {PO4} groups, exhibiting unprecedented nanosized ship-shaped clusters. The magnetic measurements reveal that compound 1 exhibits dominant antiferromagnetic interactions. Additionally, pyridine and imidazole ligands enhance the delocalized electron effects of clusters, and the third-order nonlinear-optical response of compound 1 is excellent.

12.
Chemistry ; 21(8): 3137, 2015 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-25470812

RESUMEN

Invited for the cover of this issue is the group of Hua Mei and Yan Xu at Nanjing Tech University, China. The image depicts star-like {Tb26 } clusters, which are simplified as blue balls, and Ag atoms, which are distributed in the MOF structure uniformly to give a lanthanide-MOF structure with good optical properties. Read the full text of the article at 10.1002/chem.201405178.

13.
Chemistry ; 21(8): 3234-41, 2015 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-25487542

RESUMEN

Two Ln26 @CO3 (Ln=Dy and Tb) cluster-based lanthanide-transition-metal-organic frameworks (Ln MOFs) formulated as [Dy26 Cu3 (Nic)24 (CH3 COO)8 (CO3 )11 (OH)26 (H2 O)14 ]Cl ⋅3 H2 O (1; HNic=nicotinic acid) and [Tb26 NaAg3 (Nic)27 (CH3 COO)6 (CO3 )11 (OH)26 Cl(H2 O)15 ]⋅7.5 H2 O (2) have been successfully synthesized by hydrothermal methods and characterized by IR, thermogravimetric analysis (TGA), elemental analysis, and single X-ray diffraction. Compound 1 crystallizes in the monoclinic space group Cc with a=35.775(12) Å, b=33.346(11) Å, c=24.424(8) Å, ß=93.993(5)°, V=29065(16) Å(3) , whereas 2 crystallizes in the triclinic space group P$\bar 1$ with a=20.4929(19) Å, b=24.671(2) Å, c=29.727(3) Å, α=81.9990(10)°, ß=88.0830(10)°, γ=89.9940(10)°, V=14875(2) Å(3) . Structural analysis indicates the framework of 1 is a 3D perovskite-like structure constructed out of CO3 @Dy26 building units and Cu(+) centers by means of nicotinic acid ligand bridging. In 2, however, nanosized CO3 @Tb26 units and [Ag3 Cl](2+) centers are connected by Nic(-) bridges to give rise to a 2D structure. It is worth mentioning that this kind of 4d-4f cluster-based MOF is quite rare as most of the reported analogous compounds are 3d-4f ones. Additionally, the solid-state emission spectra of pure compound 2 at room temperature suggest an efficient energy transfer from the ligand Nic(-) to Tb(3+) ions, which we called the "antenna effect". Compound 2 shows a good two-photon absorption (TPA) with a TPA coefficient of 0.06947 cm GM(-1) (1 GM=10(-50)  cm(4) s photon(-1) ), which indicates that compound 2 might be a good choice for third-order nonlinear optical materials.

14.
Inorg Chem ; 53(19): 10498-505, 2014 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-25238601

RESUMEN

Four two-dimensional fully reduced polyoxovanadates, namely, [Cd(DAP)2]4[HV(III)3V(IV)18P6O60(DAP)3(HOCH2CH2OH)]·10H2O (1), [Cd(DAP)2]4[HV(III)3V(IV)18P6O60(DAP)3(CH3OH)]·11H2O (2), [Cd(DAP)2]4[HV(III)3V(IV)18P6O60(DAP)3(CH3CH2OH)]·4H2O (3) and Co(III)(DAP)3[Co(II)(DAP)2]3[V(III)3V(IV)18P6O60(DAP)3(HOCH2CH2OH)]·14H2O (4) were synthesized by virtue of the reducing power of alkylamine in hydrothermal conditions. Single-crystal X-ray structural analysis, magnetic measurement, IR spectroscopy, elemental analysis, and thermogravimetric measurements were performed to analyze the structures and properties of these four compounds. Structural analysis indicates that the four compounds contain the same huge low-valent vanadium oxide anion cages [V(III)3V(IV)18P6O60(DAP)3](9-), and the cages can catch different guest molecules. Four cages are linked by Co or Cd atoms to form a four-membered ring, while adjacent four-membered rings are connected to each other by sharing edges to make an inorganic-organic hybrid layer. The magnetic susceptibility measurements of four compounds indicate ferrimagnetic interactions between vanadium ions.

15.
Inorg Chem ; 53(6): 2757-9, 2014 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-24559131

RESUMEN

A dimeric Keggin polyoxometalate, [Cu(bpy)(µ2-OH)]4[(H2O)(bpy)2HPW11Cu2O39]2·2CH3CH2OH·10H2O (1), constructed from two dicopper(II)-substituted monovacant Keggin polyoxoanions bridged by a Cu4 cluster, has been hydrothermally synthesized. Magnetic analysis indicates predominantly an antiferromagnetic interaction between copper(II) centers. Compound 1 also shows very high catalytic activity for the esterification of phosphoric acid with equimolar lauryl alcohol to monoalkyl phosphate ester.

16.
Pan Afr Med J ; 47: 20, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38524104

RESUMEN

In this case report, we will discuss a 74-year-old female who presented with a chief complaint of abdominal pain, bloating, anorexia, and nausea for four days which preceded after catheter ablation and anhydrous ethanol infusion vein of Marshall (VOM) one month prior. She was admitted and treated as a general patient in the general ward. After hospital admission, a pericardiocentesis was guided by B-scan ultrasonography, resulting in the extraction of 20ml of pericardial effusion, followed by catheterization for drainage. The key takeaway in this report is that anhydrous ethanol infusion VOM may not always be without risks. Hence, during the procedure, it is imperative to carefully administer the appropriate volume of anhydrous ethanol into the VOM to prevent vessel damage and associated complications.


Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Pericarditis , Femenino , Humanos , Anciano , Fibrilación Atrial/cirugía , Etanol/efectos adversos , Infusiones Intravenosas , Vasos Coronarios/cirugía , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos
17.
J Biomol Struct Dyn ; : 1-13, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38345053

RESUMEN

Pigment epithelium-derived factor (PEDF) could bind to vascular endothelial growth factor receptor 2 (VEGFR2) and inhibit its activation induced by VEGF. But how PEDF affects VEGFR2 pathway is still poorly understood. In this study, we elucidated the precise mechanism underlying the interaction between PEDF and VEGFR2, and subsequently corroborated our findings using a rat AMI model. PEDF prevented endocytosis of VE-cadherin induced by hypoxia, thereby protecting the endothelium integrity. A three-dimensional model of the VEGFR2-PEDF complex was constructed by protein-protein docking method. The results showed that the VEGFR2-PEDF complex was stable during the simulation. Hydrogen bonds, binding energy and binding modes were analyzed during molecular dynamics simulations, which indicated that hydrogen bonds and hydrophobic interactions were important for the recognition of VEGFR2 with PEDF. In addition, the results from exudation of fibrinogen suggested that PEDF inhibits vascular leakage in acute myocardial infarction and confirmed the critical role of key amino acids in the regulation of endothelial cell permeability. This observation is also supported by echocardiography studies showing that the 34mer peptide sustained cardiac function during acute myocardial infarction. Besides, PEDF and 34mer could inhibit the aggregation of myofiber in the heart and promoted the formation of a dense cell layer in cardiomyocytes, which suggested that PEDF and 34mer peptide protect against AMI-induced cardiac dysfunction. These results suggest that PEDF inhibits the phosphorylation of downstream proteins, thereby preventing vascular leakage, which provides a new therapeutic direction for the treatment of acute myocardial infarction.Communicated by Ramaswamy H. Sarma.

18.
Int J Gen Med ; 16: 2653-2662, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37384115

RESUMEN

Objective: To investigate the influence of shikonin (SK) on the formation of Candida albicans biofilms and discuss the possible mechanism. Methods: The inhibition of the formation of C. albicans biofilms by SK was observed by scanning electron microscopy. A silicone film method and a water-hydrocarbon two-phase assay were performed to investigate the effects of SK on cell adhesion. Real-time reverse-transcription polymerase chain reaction was used to analyse the expression of genes related to cell adhesion and Ras1-cyclic adenosine monophosphate (cAMP) - enhanced filamentous growth protein 1 (Efg1) signalling pathway. Finally, the level of cAMP in C. albicans was detected and exogenous cAMP rescue experiment was conducted. Results: The results showed that SK could destroy the typical three-dimensional structure of the biofilms, inhibit cell surface hydrophobicity and cell adhesion, downregulate the expression of Ras1-cAMP-Efg1 signalling pathway-related genes (ECE1, HWP1, ALS3, RAS1, CYR1, EFG1 and TEC1) and effectively reduce the production of key messenger cAMP in the Ras1-cAMP-Efg1 pathway. Meanwhile, exogenous cAMP reversed the inhibitory effect of SK on biofilms formation. Conclusion: Our results suggest that SK exhibits potential anti-C. albicans biofilms effects related to the inhibition of Ras1-cAMP-Efg1 pathway.

19.
Int J Pharm ; 640: 123050, 2023 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-37201764

RESUMEN

Lipid nanoparticles (LNPs) have demonstrated efficacy and safety for mRNA vaccine administration by intramuscular injection; however, the pulmonary delivery of mRNA encapsulated LNPs remains challenging. The atomization process of LNPs will cause shear stress due to dispersed air, air jets, ultrasonication, vibrating mesh etc., leading to the agglomeration or leakage of LNPs, which can be detrimental to transcellular transport and endosomal escape. In this study, the LNP formulation, atomization methods and buffer system were optimized to maintain the LNP stability and mRNA efficiency during the atomization process. Firstly, a suitable LNP formulation for atomization was optimized based on the in vitro results, and the optimized LNP formulation was AX4, DSPC, cholesterol and DMG-PEG2K at a 35/16/46.5/2.5 (%) molar ratio. Subsequently, different atomization methods were compared to find the most suitable method to deliver mRNA-LNP solution. Soft mist inhaler (SMI) was found to be the best for pulmonary delivery of mRNA encapsulated LNPs. The physico-chemical properties such as size and entrapment efficiency (EE) of the LNPs were further improved by adjusting the buffer system with trehalose. Lastly, the in vivo fluorescence imaging of mice demonstrated that SMI with proper LNPs design and buffer system hold promise for inhaled mRNA-LNP therapies.


Asunto(s)
Lípidos , Nanopartículas , Ratones , Animales , Lípidos/química , ARN Mensajero , Liposomas , Endosomas , Nanopartículas/química , ARN Interferente Pequeño
20.
Biol Pharm Bull ; 35(11): 1956-63, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-23123467

RESUMEN

Our study showed that Shikonin (SK) could provide an action against almost all Candida albicans isolates tested. More importantly, to some Fluconazole (FCZ)-resistant Candida albicans, the action of SK (MIC(80) value 4 µg/mL) was shown to be >16 times higher than that of FCZ (MIC(80) >64 µg/mL). To clarify the mechanism underlying this action, we performed a comparative study in untreated control C. albicans and C. albicans treated with SK. In this study, we found that SK treatment increased generation of endogenous reactive oxygen species (ROS) and decreased mitochondrial membrane potential. Furthermore, anti-oxidants N-acetylcysteine (NAC) and glutathione (GSH) could reduce the antifungal activity of SK significantly in C. albicans. Our analyses also identified 9 differentially expressed genes, which were related to glycolysis-related genes (CDC19 and HXK2), fermentation-related genes (ALD5 and ADH1), antioxidant defense-related genes (SOD2 and SOD5), thioredoxin reductase-related gene (TRR1), mitochondrial respiratory electron transport chain-related gene (MRF1) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidoreductase-related gene (EBP1). These results suggest that mitochondrial aerobic respiration shift and endogenous ROS augmentation contribute to the action of SK against C. albicans.


Asunto(s)
Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Naftoquinonas/farmacología , Acetilcisteína/farmacología , Candida albicans/crecimiento & desarrollo , Regulación Fúngica de la Expresión Génica/efectos de los fármacos , Genes Fúngicos/genética , Glutatión/farmacología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Especies Reactivas de Oxígeno/metabolismo
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