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1.
Adv Sci (Weinh) ; : e2403107, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38704679

RESUMEN

Uveal melanoma (UM) is a leading intraocular malignancy with a high 5-year mortality rate, and radiotherapy is the primary approach for UM treatment. However, the elevated lactic acid, deficiency in ROS, and hypoxic tumor microenvironment have severely reduced the radiotherapy outcomes. Hence, this study devised a novel CoMnFe-layered double oxides (LDO) nanosheet with multienzyme activities for UM radiotherapy enhancement. On one hand, LDO nanozyme can catalyze hydrogen peroxide (H2O2) in the tumor microenvironment into oxygen and reactive oxygen species (ROS), significantly boosting ROS production during radiotherapy. Simultaneously, LDO efficiently scavenged lactic acid, thereby impeding the DNA and protein repair in tumor cells to synergistically enhance the effect of radiotherapy. Moreover, density functional theory (DFT) calculations decoded the transformation pathway from lactic to pyruvic acid, elucidating a previously unexplored facet of nanozyme activity. The introduction of this innovative nanomaterial paves the way for a novel, targeted, and highly effective therapeutic approach, offering new avenues for the management of UM and other cancer types.

2.
Food Chem X ; 22: 101278, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38524781

RESUMEN

To clarify the mechanism of lower temperatures promoted the solidification of preserved egg yolk, the effects of temperature (4 °C, 10 °C and 25 °C) on the physicochemical properties, microstructure and protein structure of preserved egg yolk were studied. Results showed that the exterior egg yolk (EEY) exhibited higher pH, hardness and free sulfhydryl content at low-temperature pickling. The microstructure showed that the EEY gradually formed a denser gel network structure at lower temperatures. Electrophoresis results and Fourier transform infrared spectroscopy (FTIR) indicated that there were different degrees of protein degradation and cross-linking of proteins in the IEY (the interior egg yolk) and EEY and the decrease of ß-sheets in the secondary structure was accompanied by an increase of ß-turns during the formation of egg yolk gels. These results indicated that egg yolk solidification was faster and denser gel structure at 4 °C and 10 °C.

3.
Adv Sci (Weinh) ; : e2310189, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38468446

RESUMEN

Metal organic framework (MOF) films have attracted abundant attention due to their unique characters compared with MOF particles. But the high-temperature reaction and solvent corrosion limit the preparation of MOF films on fragile substrates, hindering further applications. Fabricating macro-sized continuous free-standing MOF films and transferring them onto fragile substrates are a promising alternative but still challenging. Here, a universal strategy to prepare transferrable macro-sized continuous free-standing MOF films with the assistance of oxide nanomembranes prepared by atomic layer deposition and studied the growth mechanism is developed. The oxide nanomembranes serve not only as reactant, but also as interfacial layer to maintain the integrality of the free-standing structure as the stacked MOF particles are supported by the oxide nanomembrane. The centimeter-scale free-standing MOF films can be transferred onto fragile substrates, and all in one device for glucose sensing is assembled. Due to the strong adsorption toward glucose molecules, the obtained devices exhibit outstanding performance in terms of high sensitivity, low limit of detection, and long durability. This work opens a new window toward the preparation of MOF films and MOF film-based biosensor chip for advantageous applications in post-Moore law period.

4.
Food Chem X ; 21: 101151, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38312487

RESUMEN

The influence of ultrasonic processing on the physicochemical characteristics, microstructure, and intermolecular forces of the hybrid gels obtained by heating the mixtures of different ratios of salted ovalbumin (SOVA)-cooked soybean protein isolate (CSPI) was investigated. With the growth of SOVA addition, ζ-potential in absolute value, cohesiveness, water-holding capacity (WHC), surface hydrophobicity, and the content of soluble protein of the hybrid gels decreased (P < 0.05), while the hardness, T2 relaxation time of the hybrid gels increased (P < 0.05). And the compactness of the network structure of the hybrid gel increased with the increase of SOVA addition. After being treated with ultrasound, significant increases (P < 0.05) of ζ-potential in absolute value, cohesiveness, WHC, and surface hydrophobicity of the hybrid gels were observed. In general, ultrasonic processing is one of the effective means to improve the gel properties of SOVA-CSPI hybrid gels.

6.
Mol Psychiatry ; 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38212372

RESUMEN

At the center of the hippocampal tri-synaptic loop are synapses formed between mossy fiber (MF) terminals from granule cells in the dentate gyrus (DG) and proximal dendrites of CA3 pyramidal neurons. However, the molecular mechanism regulating the development and function of these synapses is poorly understood. In this study, we showed that neurotrophin-3 (NT3) was expressed in nearly all mature granule cells but not CA3 cells. We selectively deleted the NT3-encoding Ntf3 gene in the DG during the first two postnatal weeks to generate a Ntf3 conditional knockout (Ntf3-cKO). Ntf3-cKO mice of both sexes had normal hippocampal cytoarchitecture but displayed impairments in contextual memory, spatial reference memory, and nest building. Furthermore, male Ntf3-cKO mice exhibited anxiety-like behaviors, whereas female Ntf3-cKO showed some mild depressive symptoms. As MF-CA3 synapses are essential for encoding of contextual memory, we examined synaptic transmission at these synapses using ex vivo electrophysiological recordings. We found that Ntf3-cKO mice had impaired basal synaptic transmission due to deficits in excitatory postsynaptic currents mediated by AMPA receptors but normal presynaptic function and intrinsic excitability of CA3 pyramidal neurons. Consistent with this selective postsynaptic deficit, Ntf3-cKO mice had fewer and smaller thorny excrescences on proximal apical dendrites of CA3 neurons and lower GluR1 levels in the stratum lucidum area where MF-CA3 synapses reside but normal MF terminals, compared with control mice. Thus, our study indicates that NT3 expressed in the dentate gyrus is crucial for the postsynaptic structure and function of MF-CA3 synapses and hippocampal-dependent memory.

7.
Trop Life Sci Res ; 34(3): 1-22, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37860094

RESUMEN

Malaysia is home to a number of hot springs that are rich in microbial diversity including the photosynthetic cyanobacteria. Although this microbial community has been characterised based on metagenomics approach, the culturable thermophilic isolates have not been isolated and characterised extensively. Compared to the mesophiles, information on plant growth promoting (PGP) properties of these thermophiles remain largely untapped. As the amount of arable land for microbial bioprospecting is decreasing due to extensive human activities, the search for alternative source for microbial strains with PGP properties is important for the development of potential biofertilisers. This study sought to isolate and characterise culturable cyanobacteria strains from two local hot springs - Sungai Klah (SK) and Lubuk Timah (LT) located in Perak using morphological and molecular methods. The IAA production from the axenic cultures were measured. The PGP properties were also measured by priming the rice seeds with cyanobacterial water extracts. A total of six strains were isolated from both hot springs. Strains LTM and LTW from LT were identified as Leptolyngbya sp. whereas strains SEM, SEH, STH and STM were identified as Thermosynechococcus elongatus. All six strains produced IAA ranged from 670.10 pg/µL to 2010 pg/µL. The water extracts were found to increase the seed amylase activity of the rice seeds from 5th day of germination (DAG) to 10th DAG. In general, the IAA production and increased seed amylase activity might have contributed in enhancing the longest root length, shoot length and root-to-shoot (RS) ratio. To conclude, the thermophilic cyanobacteria from hot springs can be further exploited as a novel source of PGP microbes for the development of biofertilsers.

8.
BMC Complement Med Ther ; 23(1): 307, 2023 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-37667314

RESUMEN

BACKGROUND: Allergy is an inflammatory disorder affecting around 20% of the global population. The adverse effects of current conventional treatments give rise to the increased popularity of using natural food products as complementary and alternative medicine against allergic diseases. Stingless bee honey, commonly known as Kelulut honey (KH) in Malaysia, has been used locally as a traditional remedy to relieve cough and asthma. This study evaluated the anti-allergic potential of KH collected from four different botanical sources on phorbol ester 12-myristate-3-acetate and calcium ionophore-activated human mast cells. METHODS: The present study examined the inhibitory effects of all collected honey on the release of selected inflammatory mediators, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-4, IL-6, IL-8, histamine, and ß-hexosaminidase in an activated HMC. Besides that, all honey's total phenolic content (TPC) was also examined, followed by using liquid chromatography with tandem mass spectrometry (LC-MS/MS) to identify the phytochemicals in the honey. Further examination of the identified phytochemicals on their potential interaction with selected signaling molecules in an activated mast cell was conducted using computational methods. RESULTS: The results indicated that there were significant inhibitory effects on all selected inflammatory mediators' release by KH sourced from bamboo (BH) and rubber tree (RH) at 0.5% and 1%, but not KH sourced from mango (AH) and noni (EH). BH and RH were found to have higher TPC values and were rich in their phytochemical profiles based on the LC-MS/MS results. Computational studies were employed to determine the possible molecular target of KH through molecular docking using HADDOCK and PRODIGY web servers. CONCLUSIONS: In short, the results indicated that KH possesses anti-allergic effects towards an activated HMC, possibly by targeting downstream MAPKs. However, their anti-allergic effects may vary according to their botanical sources. Nevertheless, the present study has provided insight into the potential application of stingless bee honey as a complementary and alternative medicine to treat various allergic diseases.


Asunto(s)
Antialérgicos , Miel , Hipersensibilidad , Humanos , Abejas , Animales , Antialérgicos/farmacología , Mastocitos , Degranulación de la Célula , Cromatografía Liquida , Simulación del Acoplamiento Molecular , Espectrometría de Masas en Tándem
9.
Int Immunopharmacol ; 123: 110770, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37562293

RESUMEN

Rheumatoid arthritis (RA) is a chronic autoimmune disease that occurs mainly in synovial joints, causing synovial inflammation and joint injury. If diagnosed and treated in time, the disease can be well controlled. However, in clinical practice, patients often fail to get timely and effective treatment due to misdiagnosis, missed diagnosis, and other reasons, resulting in deterioration of the condition and poor prognosis, seriously affecting the patient's quality of life. So far, the pathogenesis of RA is still unclear. In recent years, it has been found that the imbalance of cytokines plays a vital role in the occurrence and development of RA. Most RA-related cytokines are produced by immune cells, which bind to the specific receptors of effector cells through paracrine and autocrine pathways. The effect of cytokines on inflammation can be divided into pro-inflammatory and anti-inflammatory factors. When the impact of pro-inflammatory factors is more significant than anti-inflammatory factors, the condition of RA will be aggravated, resulting in more inflammatory severe reactions and immune disorders. Interleukin-33 (IL-33) is a new member of the interleukin-1(IL-1) family, and its receptor is suppression of tumorigenicity 2 (ST2). IL-33 plays a vital role in immune diseases such as RA by promoting a series of biochemical reactions in macrophages, mast cells, granulocytes, and other cells. This article aims to summarize the research progress of IL-33 in the pathogenesis of RA in recent years, discuss its role in the pathogenesis of RA, and provide new ideas for the prevention and treatment of RA in the future.


Asunto(s)
Artritis Reumatoide , Interleucina-33 , Humanos , Citocinas , Inflamación , Interleucina-1 , Calidad de Vida
10.
Adv Sci (Weinh) ; 10(27): e2300470, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37505480

RESUMEN

Myocardial infarction (MI) causes excessive damage to the myocardium, including the epicardium. However, whether pluripotent stem cell-derived epicardial cells (EPs) can be a therapeutic approach for infarcted hearts remains unclear. Here, the authors report that intramyocardial injection of human embryonic stem cell-derived EPs (hEPs) at the acute phase of MI ameliorates functional worsening and scar formation in mouse hearts, concomitantly with enhanced cardiomyocyte survival, angiogenesis, and lymphangiogenesis. Mechanistically, hEPs suppress MI-induced infiltration and cytokine-release of inflammatory cells and promote reparative macrophage polarization. These effects are blocked by a type I interferon (IFN-I) receptor agonist RO8191. Moreover, intelectin 1 (ITLN1), abundantly secreted by hEPs, interacts with IFN-ß and mimics the effects of hEP-conditioned medium in suppression of IFN-ß-stimulated responses in macrophages and promotion of reparative macrophage polarization, whereas ITLN1 downregulation in hEPs cancels beneficial effects of hEPs in anti-inflammation, IFN-I response inhibition, and cardiac repair. Further, similar beneficial effects of hEPs are observed in a clinically relevant porcine model of reperfused MI, with no increases in the risk of hepatic, renal, and cardiac toxicity. Collectively, this study reveals hEPs as an inflammatory modulator in promoting infarct healing via a paracrine mechanism and provides a new therapeutic approach for infarcted hearts.


Asunto(s)
Células Madre Embrionarias Humanas , Infarto del Miocardio , Porcinos , Ratones , Humanos , Animales , Miocardio , Miocitos Cardíacos , Infarto del Miocardio/tratamiento farmacológico , Macrófagos
11.
ACS Biomater Sci Eng ; 9(7): 4197-4207, 2023 07 10.
Artículo en Inglés | MEDLINE | ID: mdl-37378535

RESUMEN

There is an evident advantage in personalized customization of orthopedic implants by 3D-printed titanium (Ti) and its alloys. However, 3D-printed Ti alloys have a rough surface structure caused by adhesion powders and a relatively bioinert surface. Therefore, surface modification techniques are needed to improve the biocompatibility of 3D-printed Ti alloy implants. In the present study, porous Ti6Al4V scaffolds were manufactured by a selective laser melting 3D printer, followed by sandblasting and acid-etching treatment and atomic layer deposition (ALD) of tantalum oxide films. SEM morphology and surface roughness tests confirmed that the unmelted powders adhered on the scaffolds were removed by sandblasting and acid-etching. Accordingly, the porosity of the scaffold increased by about 7%. Benefiting from the self-limitation and three-dimensional conformance of ALD, uniform tantalum oxide films were formed on the inner and outer surfaces of the scaffolds. Zeta potential decreased by 19.5 mV after depositing tantalum oxide films. The in vitro results showed that the adhesion, proliferation, and osteogenic differentiation of rat bone marrow mesenchymal stem cells on modified Ti6Al4V scaffolds were significantly enhanced, which may be ascribed to surface structure optimization and the compatibility of tantalum oxide. This study provides a strategy to improve the cytocompatibility and osteogenic differentiation of porous Ti6Al4V scaffolds for orthopedic implants.


Asunto(s)
Osteogénesis , Titanio , Ratas , Animales , Titanio/farmacología , Titanio/química , Polvos , Impresión Tridimensional , Aleaciones
12.
Adv Mater ; 35(20): e2211632, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36868183

RESUMEN

Molecular fluorophores with the second near-infrared (NIR-II) emission hold great potential for deep-tissue bioimaging owing to their excellent biocompatibility and high resolution. Recently, J-aggregates are used to construct long-wavelength NIR-II emitters as their optical bands show remarkable red shifts upon forming water-dispersible nano-aggregates. However, their wide applications in the NIR-II fluorescence imaging are impeded by the limited varieties of J-type backbone and serious fluorescence quenching. Herein, a bright benzo[c]thiophene (BT) J-aggregate fluorophore (BT6) with anti-quenching effect is reported for highly efficient NIR-II bioimaging and phototheranostics. The BT fluorophores are manipulated to have Stokes shift over 400 nm and aggregation-induced emission (AIE) property for conquering the self-quenching issue of the J-type fluorophores. Upon forming BT6 assemblies in an aqueous environment, the absorption over 800 nm and NIR-II emission over 1000 nm are boosted for more than 41 and 26 folds, respectively. In vivo visualization of the whole-body blood vessel and imaging-guided phototherapy results verify that BT6 NPs are excellent agent for NIR-II fluorescence imaging and cancer phototheranostics. This work develops a strategy to construct bright NIR-II J-aggregates with precisely manipulated anti-quenching properties for highly efficient biomedical applications.


Asunto(s)
Nanopartículas , Neoplasias , Humanos , Colorantes Fluorescentes/farmacología , Fototerapia , Imagen Óptica/métodos
13.
3 Biotech ; 13(2): 71, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36742448

RESUMEN

Cyanobacteria bioactive compounds are chemical treasure troves for product discovery and development. The wound healing effects and antioxidant capacities of water extracts from Nostoc NIES-2111_MUM004 were evaluated via in vitro wound scratch assay and three antioxidant assays respectively. Results showed that the water extracts were protein-rich and exhibited good antioxidant properties in ABTS radical scavenging (11.27 ± 0.205 mg TAE g-1 extract), Ferric reducing antioxidant power (1652.71 ± 110.71 mg TAE g-1 extract) and ß-carotene bleaching assay (354.90 ± 31.80 mg TAE g-1 extract). Also, extracts were non-cytotoxic in concentrations up to 250 µg/mL as reflected in cytotoxicity assay. Importantly, water extracts showed considerable proliferation and migration activity at 125 µg/mL with wound closure rate as high as 42.67%. Statistical correlation revealed no significant relationship (p > 0.05) between protein fraction and the wound healing properties, confirming that phycobiliproteins were not solely responsible for wound healing activities. Subsequent Q-TOF-LCMS analysis identified six protein families involved in enhancing the proliferation and migration of epithelial cells. These findings are antecedent in the uncovering of continuous supplies of bioactive compounds from new and sustainable sources. Ultimately, enriching the microalgae menu for applications in pharmaceutical, nutraceutical and cosmeceuticals.

14.
Plast Reconstr Surg ; 152(1): 117-123, 2023 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-36735820

RESUMEN

BACKGROUND: Digital necrosis (DN) is a serious complication after replantation. However, predisposing factors, as reported less, remain controversial. The purpose of this study was to explore risk factors of necrosis after single-digit replantation by means of a retrospective study. METHODS: Patients who underwent single-digit replantations in our hospital between June of 2014 and October of 2020 were included. The authors regarded DN as the failure group and digital survival as the success group. The factors were conducted by univariate and multivariate analysis. RESULTS: The survival rate in our study was 78.8% (745 of 946). The results of univariate analysis showed that there were significant differences in the levels of D-dimer (first), menstrual cycle, injury level, and starting and finishing time of surgery between different groups. In multivariate analysis, age, injury level, duration of surgery, and D-dimer (first) were identified as the risk factors for DN in the entire and male population. In addition, regarding male patients, ischemia time was also found to be a risk factor for DN. In terms of female patients, the menstrual period and menopause were related to DN. CONCLUSIONS: Many factors, including age, ischemia time, injury level, menstrual period, menopause, and duration of surgery, were related to DN after digital replantation. D-dimer (first) was first found as a predicted factor for DN. In addition, these results also showed that the starting and ending times of surgery were associated with DN by univariate analysis. Preoperative measures should be taken to lower the incidence of DN. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.


Asunto(s)
Amputación Traumática , Traumatismos de los Dedos , Humanos , Masculino , Femenino , Estudios Retrospectivos , Amputación Traumática/cirugía , Amputación Traumática/etiología , Traumatismos de los Dedos/cirugía , Reimplantación/métodos , Necrosis/etiología , Isquemia/etiología
15.
ACS Appl Mater Interfaces ; 15(9): 12005-12016, 2023 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-36827513

RESUMEN

Ever-evolving advancements in films have fueled many of the developments in the field of electrochemical sensors. For biosensor application platforms, the fabrication of metal-organic framework (MOF) films on microscopically structured substrates is of tremendous importance. However, fabrication of MOF film-based electrodes always exhibits unsatisfactory performance, and the mechanisms of the fabrication and sensing application of the corresponding composites also need to be explored. Here, we report the fabrication of conformal MIL-53 (Fe) films on carbonized natural seaweed with the assistance of an oxide nanomembrane and a potential-dependent electrochemical dopamine (DA) sensor. The geometry and structure of the composite can be conveniently tuned by the experimental parameters, while the sensing performance is significantly influenced by the applied potential. The obtained sensor demonstrates ultrahigh sensitivity, a wide linear range, a low limit of detection, and a good distinction between DA and ascorbic acid at an optimized potential of 0.3 V. The underneath mechanism is investigated in detail with the help of theoretical calculations. This work bridges the natural material and MOF films and is promising for future biosensing applications.


Asunto(s)
Técnicas Biosensibles , Estructuras Metalorgánicas , Estructuras Metalorgánicas/química , Carbono/química , Dopamina/química , Óxidos , Electrodos , Técnicas Electroquímicas
16.
Angew Chem Int Ed Engl ; 62(10): e202215226, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36593222

RESUMEN

Rationally tuning the emission position and narrowing the full width at half-maximum (FWHM) of an emitter is of great importance for many applications. By synergistically improving rigidity, strengthening the resonant strength, inhibiting molecular bending and rocking, and destabilizing the HOMO energy level, a deep-blue emitter (CZ2CO) with a peak wavelength of 440 nm and an ultranarrow spectral FWHM of 16 nm (0.10 eV) was developed via intramolecular cyclization in a carbonyl/N resonant core (QAO). The dominant υ0-0 transition character of CZ2CO gives a Commission Internationale de I'Éclairage coordinates (CIE) of (0.144, 0.042), nicely complying with the BT.2020 standard. Moreover, a hyper-fluorescent device based on CZ2CO shows a high maximum external quantum efficiency (EQEmax ) of 25.6 % and maintains an EQE of 22.4 % at a practical brightness of 1000 cd m-2 .

17.
Angew Chem Int Ed Engl ; 62(6): e202214281, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36314420

RESUMEN

The development of photoinduced luminescent radicals with dynamic emission color is still challenging. Herein we report a novel molecular radical system (TBIQ) that shows photo-controllable luminescence, leading to a wide range of ratiometric color changes via light excitation. The conjugated skeleton of TBIQ is decorated with steric-demanding tertiary butyl groups that enable appropriate intermolecular interaction to make dynamic intermolecular coupling possible for controllable behaviors. We reveal that the helicenic pseudo-planar conformation of TBIQ experiences a planarization process after light excitation, leading to more compactly stacked supermolecules and thus generating radicals via intermolecular charge transfer. The photo-controllable luminescent radical system is employed for a high-level information encryption application. This study may offer unique insight into molecular dynamic motion for optical manufacturing and broaden the scope of smart-responsive materials for advanced applications.

18.
J Ethnopharmacol ; 303: 116003, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36464074

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Allergy is mediated by the crosslinking of immunoglobulins (Ig) -E or -G to their respective receptors, which degranulates mast cells, macrophages, basophils, or neutrophils, releasing allergy-causing mediators. The removal of these mediators such as histamine, platelet-activating factor (PAF) and interleukins (ILs) released by effector cells will alleviate allergy. Clinacanthus nutans (C. nutans), an herbal plant in Southeast Asia, is used traditionally to treat skin rash, an allergic symptom. Previously, we have reported that C. nutans aqueous leaves extract (CNAE) was able to suppress the release of ß-hexosaminidase and histamine but not interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-α) in the IgE-induced mast cell degranulation model at 5 mg/mL and above. We also found that CNAE could protect rats against ovalbumin-challenged active systemic anaphylaxis (OVA-ASA) through the downregulation and upregulation of certain metabolites using proton nuclear magnetic resonance (1H-NMR) metabolomics approach. AIM OF THE STUDY: As allergy could be mediated by both IgE and IgG, we further evaluated the anti-allergy potential of CNAE in both in vitro model of IgG-induced macrophage activation and in vivo anaphylaxis models to further dissect the mechanism of action underlying the anti-allergic properties of CNAE. MATERIAL & METHODS: The anti-allergy potential of CNAE was evaluated in in vivo anaphylaxis models of ovalbumin-challenged active systemic anaphylaxis (OVA-ASA) and IgE-challenged passive systemic anaphylaxis (PSA) using Sprague Dawley rats as well as IgG-challenged passive systemic anaphylaxis (IgG-PSA) using C57BL/6 mice. Meanwhile, in vitro model of IgG-induced macrophage activation model was performed using IC-21 macrophages. The release of soluble mediators from both IgE and IgG-mediated pathways were measured using enzyme-linked immunosorbent assay (ELISA). The signaling molecules targeted by CNAE were identified by performing Western blot. RESULTS: IgG, platelet-activating factor (PAF) and IL-6 was suppressed by CNAE in OVA-ASA, but not IgE. In addition, CNAE significantly suppressed PAF and IL-6 in IgG-PSA but did not suppress histamine, IL-4 and leukotrienes C4 (LTC4) in IgE-PSA. CNAE also inhibited IL-6 and TNF-α by inhibiting the phosphorylation of ERK1/2 in the IgG-induced macrophage activation model. CONCLUSION: Overall, our findings supported that CNAE exerts its anti-allergic properties by suppressing the IgG pathway and its mediators by inhibiting ERK1/2 phosphorylation, thus providing scientific evidence supporting its traditional use in managing allergy.


Asunto(s)
Anafilaxia , Antialérgicos , Ratones , Ratas , Animales , Anafilaxia/etiología , Antialérgicos/farmacología , Antialérgicos/uso terapéutico , Interleucina-4/metabolismo , Ratas Sprague-Dawley , Histamina/metabolismo , Ovalbúmina , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Ratones Endogámicos C57BL , Inmunoglobulina E/metabolismo , Factor de Activación Plaquetaria/metabolismo , Factor de Activación Plaquetaria/uso terapéutico , Inmunoglobulina G , Mastocitos
19.
Small ; 19(5): e2204852, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36464630

RESUMEN

The repair of bone defects caused by osteosarcoma resection remains a clinical challenge because of the tumor recurrence and bacterial infection. Combining tumor and bacterial therapy with bone regeneration properties in bone implants is a promising strategy for the treatment of osteosarcoma. Here, a layer of MgO/FeOx nanosheet is constructed on the Ti implant to prevent tumor recurrence and bacterial infection, while simultaneously accelerating bone formation. This MgO/FeOx double metal oxide demonstrates good peroxidase activity to catalyze H2 O2 , which is rich in tumor microenvironment, to form reactive oxygen species (ROS), and shows good photothermal conversion capacity to produce photothermal effect, thus synergistically killing tumor cells and eliminating tumor tissue. In addition, it generates a local alkaline surface microenvironment to inhibit the energy metabolism of bacteria to enhance the photothermal antibacterial effect. Furthermore, benefiting from the generation of a Mg ion-containing alkaline microenvironment, this MgO/FeOx film can promote the osteogenic differentiation of osteoblast and angiogenesis of vascular endothelial cells in vitro as well as accelerated bone formation in vivo. This study proposes a multifunctional platform for integrating tumor and bacterial therapy and bone regeneration, which has good application prospects for the treatment of osteosarcoma.


Asunto(s)
Infecciones Bacterianas , Neoplasias Óseas , Osteosarcoma , Humanos , Titanio/farmacología , Osteogénesis , Óxido de Magnesio , Células Endoteliales , Recurrencia Local de Neoplasia , Regeneración Ósea , Osteosarcoma/terapia , Neoplasias Óseas/terapia , Microambiente Tumoral
20.
Bioact Mater ; 20: 472-488, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35800406

RESUMEN

Implantable biomaterials are widely used in the curative resection and palliative treatment of various types of cancers. However, cancer residue around the implants usually leads to treatment failure with cancer reoccurrence. Postoperation chemotherapy and radiation therapy are widely applied to clear the residual cancer cells but induce serious side effects. It is urgent to develop advanced therapy to minimize systemic toxicity while maintaining efficient cancer-killing ability. Herein, we report a degenerate layered double hydroxide (LDH) film modified implant, which realizes microenvironment-responsive electrotherapy. The film can gradually transform into a nondegenerate state and release holes. When in contact with tumor cells or bacteria, the film quickly transforms into a nondegenerate state and releases holes at a high rate, rendering the "electrocution" of tumor cells and bacteria. However, when placed in normal tissue, the hole release rate of the film is much slower, thus, causing little harm to normal cells. Therefore, the constructed film can intelligently identify and meet the physiological requirements promptly. In addition, the transformation between degenerate and nondegenerate states of LDH films can be cycled by electrical charging, so their selective and dynamic physiological functions can be artificially adjusted according to demand.

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