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1.
Biochem Biophys Res Commun ; 719: 150027, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38749089

RESUMO

Aging is a complex, degenerative process associated with various metabolic abnormalities. Ginsenosides (GS) is the main active components of Panax ginseng, which has anti-aging effects and improves metabolism. However, the anti-aging effect and the mechanism of GS in middle-aged mice has not been elucidated. In this study, GS after 3-month treatment significantly improved the grip strength, fatigue resistance, cognitive indices, and cardiac function of 15-month-old mice. Meanwhile, GS treatment reduced the fat content and obviously inhibited histone H2AX phosphorylation at Ser 139 (γ-H2AX), a marker of DNA damage in major organs, especially in the heart and liver. Further, the correlation analysis of serum metabolomics combined with aging phenotype suggested that myo-inositol (MI) upregulated by GS was positively correlated with left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), the main indicators of cardiac function. More importantly, liver tissue metabolomic analysis showed that GS increased MI content by promoting the synthesis pathway from phosphatidylcholine (PC) to MI for the inhibition of liver aging. Finally, we proved that MI reduced the percentage of senescence-associated ß-galactosidase staining, γ-H2AX immunofluorescence staining, p21 expression, and the production of reactive oxygen species in H2O2-induced cardiomyocytes. These results suggest that GS can enhance multiple organ functions, especially cardiac function for promoting the healthspan of aging mice, which is mediated by the conversion of PC to MI in the liver and the increase of MI level in the serum. Our study might provide new insights into the potential mechanisms of ginsenosides for prolonging the healthspan of natural aging mice.

2.
Nanoscale ; 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38695774

RESUMO

For the electroreduction of carbon dioxide into high value-added chemicals, highly active and selective catalysts are crucial, and metallic silver is one of the most intriguing candidate materials available at a reasonable cost. Herein, through a novel two-step operation of Ag paste/SBA-15 coating and HF etching, porous silver films on a commercial carbon paper with a waterproofer (p-Ag/CP) could be easily fabricated on a large scale as highly efficient carbon dioxide reduction reaction (CO2RR) electrocatalysts with a CO Faraday efficiency (FECO) as high as 96.7% at -1.0 V vs. the reversible hydrogen electrode (RHE), and it still reaches up to 90% FECO over applied potentials ranging from -0.8 to -1.1 V vs. the RHE. Meanwhile, the membrane electrode assembly (MEA) utilizing the p-Ag/CP catalyst has achieved a current density, FECO, and stability of ∼60 mA cm-2, >91%, and 11 h, respectively. Furthermore, the assembled aqueous Zn-CO2 battery using p-Ag/CP cathode yielded a peak power density of 0.34 mW cm-2, 75 charge-discharge cycles for 25 h, and 64% FECO at 2.5 mA cm-2. Compared with flat Ag/CP, the significant enhancement in the CO2RR activity of p-Ag/CP was mainly attributed to the distinctive porous structure and an improved three-phase boundary, which is capable of inducing the stabilization of *COOH intermediates, increased active specific surface areas, fast electron transfer kinetic and mass transportation. Further, theoretical calculations revealed that p-Ag/CP possessed an optimized energy barrier for *COOH intermediates.

3.
Int J Biol Macromol ; 269(Pt 1): 131872, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38677706

RESUMO

The increasing incidence of obesity has led to widespread attention in the exploration of natural ingredients. Ginseng polysaccharides (PGP), the main components from Panax ginseng, have been reported potential effect to attenuate obesity and regulate lipid metabolism. In this study, we found that PGP inhibited the high-fat diet (HFD)-induced weight gain, fat ratio and fat tissue weight after 8-week administration. Serum and liver lipid analysis showed that PGP decreased the levels of triglyceride and total cholesterol, which was mediated by the inhibition of key genes for fatty acid and cholesterol metabolisms. Metabolomics studies showed that the inhibitory effect of PGP on liver lipid accumulation was significantly correlated with its regulation of citric acid cycle and lysine degradation. PGP regulated the expression of genes related to lysine degradation in both liver tissue and hepatocytes. In addition, PGP reshaped the composition of fecal microbiota at the genus and species levels in obese mice. Spearman's correlation analysis demonstrated that Staphylococcus sciuri, Staphylococcus lentus, and Pseudoflavonifractor sp. An85 may be the potential targets that PGP maintains the abundance of l-lysine against obesity. It concluded that PGP can attenuate obesity and liver lipid accumulation by regulating fecal microbiota and hepatic lysine degradation.

4.
Int J Mol Sci ; 25(5)2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38474239

RESUMO

It is well known that extreme heat events happen frequently due to climate change. However, studies examining the direct health impacts of increased temperature and heat waves are lacking. Previous reports revealed that heatstroke induced acute lung injury and pulmonary dysfunction. This study aimed to investigate whether heat exposure induced lung fibrosis and to explore the underlying mechanisms. Male C57BL/6 mice were exposed to an ambient temperature of 39.5 ± 0.5 °C until their core temperature reached the maximum or heat exhaustion state. Lung fibrosis was observed in the lungs of heat-exposed mice, with extensive collagen deposition and the elevated expression of fibrosis molecules, including transforming growth factor-ß1 (TGF-ß1) and Fibronectin (Fn1) (p < 0.05). Moreover, epithelial-mesenchymal transition (EMT) occurred in response to heat exposure, evidenced by E-cadherin, an epithelial marker, which was downregulated, whereas markers of EMT, such as connective tissue growth factor (CTGF) and the zinc finger transcriptional repressor protein Slug, were upregulated in the heat-exposed lung tissues of mice (p < 0.05). Subsequently, cell senescence examination revealed that the levels of both senescence-associated ß-galactosidase (SA-ß-gal) staining and the cell cycle protein kinase inhibitor p21 were significantly elevated (p < 0.05). Mechanistically, the cGAS-STING signaling pathway evoked by DNA damage was activated in response to heat exposure (p < 0.05). In summary, we reported a new finding that heat exposure contributed to the development of early pulmonary fibrosis-like changes through the DNA damage-activated cGAS-STING pathway followed by cellular senescence.


Assuntos
Fibrose Pulmonar , Masculino , Camundongos , Animais , Fibrose Pulmonar/metabolismo , Temperatura Alta , Camundongos Endogâmicos C57BL , Pulmão/patologia , Fator de Crescimento Transformador beta1/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Senescência Celular , Nucleotidiltransferases/metabolismo
5.
Environ Pollut ; 347: 123643, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38428793

RESUMO

Heat exposure induces excessive hyperthermia associated with systemic inflammatory response that leads to multiple organ dysfunction including acute lung injury. However, how heat impairs the lung remains elusive so far. We aimed to explore the underlying mechanism by focusing on leucine-rich repeat kinase 2 (LRRK2), which was associated with lung homeostasis. Both in vivo and in vitro models were induced by heat exposure. Firstly, heat exposure exerted core temperature (Tc) disturbance, pulmonary dysfunction, atelectasis, inflammation, impaired energy metabolism, and reduced surfactant proteins in the lung of mice. In addition, decreased LRRK2 expression and increased heat shock proteins (HSPs) 70 were observed with heat exposure in both the lung of mice and alveolar type II epithelial cells (AT2). Furthermore, LRRK2 inhibition aggravated heat exposure-initiated Tc dysregulation, injury in the lung and AT2 cells, and enhanced HSP70 expression. In conclusion, LRRK2 is involved in heat-induced acute lung injury and AT2 cell dysfunction.


Assuntos
Lesão Pulmonar Aguda , Lesão Pulmonar , Humanos , Células Epiteliais Alveolares/metabolismo , Pulmão , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/metabolismo
6.
Heliyon ; 10(5): e26441, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38455566

RESUMO

Reinjecting produced methane offers cost-efficiency and environmental benefits for enhances oil recovery. High minimum miscibility pressure (MMP) in methane-oil systems poses a challenge. To overcome this, researchers are increasingly focusing on using surfactants to reduce MMP, thus enhancing the effectiveness of methane injections for oil recovery. This study investigated the impact of pressure and temperature on the equilibrium interfacial tension of the CH4+n-decane system using molecular dynamics simulations and the vanishing interfacial tension technique. The primary goal was to assess the potential of surfactants in lowering MMP. Among four tested surfactants, ME-6 exhibited the most promise by reducing MMP by 14.10% at 373 K. Key findings include that the addition of ME-6 enriching CH4 at the interface, enhancing its solubility in n-decane, improving n-decane diffusion capacity, CH4 weakens n-decane interactions and strengthens its own interaction with n-decane. As the difference in interactions of n-decane with ME-6's ends decreases, the system trends towards a mixed phase. This research sets the stage for broader applications of mixed-phase methane injection in reservoirs, with the potential for reduced gas flaring and environmental benefits.

7.
Nature ; 626(8001): 984-989, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38326619

RESUMO

Controlled charge flows are fundamental to many areas of science and technology, serving as carriers of energy and information, as probes of material properties and dynamics1 and as a means of revealing2,3 or even inducing4,5 broken symmetries. Emerging methods for light-based current control5-16 offer particularly promising routes beyond the speed and adaptability limitations of conventional voltage-driven systems. However, optical generation and manipulation of currents at nanometre spatial scales remains a basic challenge and a crucial step towards scalable optoelectronic systems for microelectronics and information science. Here we introduce vectorial optoelectronic metasurfaces in which ultrafast light pulses induce local directional charge flows around symmetry-broken plasmonic nanostructures, with tunable responses and arbitrary patterning down to subdiffractive nanometre scales. Local symmetries and vectorial currents are revealed by polarization-dependent and wavelength-sensitive electrical readout and terahertz (THz) emission, whereas spatially tailored global currents are demonstrated in the direct generation of elusive broadband THz vector beams17. We show that, in graphene, a detailed interplay between electrodynamic, thermodynamic and hydrodynamic degrees of freedom gives rise to rapidly evolving nanoscale driving forces and charge flows under the extremely spatially and temporally localized excitation. These results set the stage for versatile patterning and optical control over nanoscale currents in materials diagnostics, THz spectroscopies, nanomagnetism and ultrafast information processing.

8.
Opt Express ; 32(2): 2058-2066, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38297743

RESUMO

Lenses with a tunable focus are highly desirable but remain a challenge. Here, we demonstrate a microwave varifocal meta-lens based on the Alvarez lens principle, consisting of two mechanically movable tri-layer metasurface phase plates with reversed cubic spatial profiles. The manufactured multilayer Alvarez meta-lens enables microwave beam collimation/focusing at frequencies centered at 7.5 GHz, and shows one octave focal length tunability when transversely translating the phase plates by 8 cm. The measurements reveal a gain enhancement up to 15 dB, 3-dB beam width down to 3.5∘, and relatively broad 3-dB bandwidth of 3 GHz. These advantageous characteristics, along with its simplicity, compactness, and lightweightness, make the demonstrated flat Alvarez meta-lens suitable for deployment in many microwave systems.

9.
Anal Chem ; 95(35): 13156-13162, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37606955

RESUMO

Herein, by introducing gold nanostars (AuNSs) as fuel core, a near-infrared-driven nanorocket (NIDNR) with pretty fast walking was exploited for ultrasensitive miRNA detection. Compared with traditional nanomaterials-comprised nanomachines (NMs), the NIDNR possesses much better kinetic and thermodynamic performance owing to the extra photothermal driving force from localized surface plasmon (LSP). Impressively, the whole reaction time of NIDNR down to 15 min was realized, which is almost more than 8 times beyond those of conventional DNA-based NMs. This way, the inherent obstacle of traditional NMs, including long reaction time and low efficiency, could be easily addressed. As a proof of concept, the NIDNR was successfully applied to develop an electrochemical biosensing platform for rapid and sensitive detection of miRNA with an LOD down to 2.95 aM and achieved the real-time assay of real biological samples from human hepatocellular carcinoma cells (MHCC97L) and HeLa, thus providing an innovative insight to design more versatile DNA nanomachines for ultimate application in biosensing platform construction and clinical sample detection.


Assuntos
Espectroscopia de Luz Próxima ao Infravermelho , Espectroscopia de Luz Próxima ao Infravermelho/instrumentação , Espectroscopia de Luz Próxima ao Infravermelho/métodos , MicroRNAs/química , Fatores de Tempo , Ouro , Nanopartículas Metálicas/química , Técnicas Biossensoriais , Técnicas Reprodutivas , Humanos , Linhagem Celular Tumoral
10.
Light Sci Appl ; 12(1): 133, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37258515

RESUMO

Nonlinear optical spectroscopies are powerful tools for investigating both static material properties and light-induced dynamics. Terahertz (THz) emission spectroscopy has emerged in the past several decades as a versatile method for directly tracking the ultrafast evolution of physical properties, quasiparticle distributions, and order parameters within bulk materials and nanoscale interfaces. Ultrafast optically-induced THz radiation is often analyzed mechanistically in terms of relative contributions from nonlinear polarization, magnetization, and various transient free charge currents. While this offers material-specific insights, more fundamental symmetry considerations enable the generalization of measured nonlinear tensors to much broader classes of systems. We thus frame the present discussion in terms of underlying broken symmetries, which enable THz emission by defining a system directionality in space and/or time, as well as more detailed point group symmetries that determine the nonlinear response tensors. Within this framework, we survey a selection of recent studies that utilize THz emission spectroscopy to uncover basic properties and complex behaviors of emerging materials, including strongly correlated, magnetic, multiferroic, and topological systems. We then turn to low-dimensional systems to explore the role of designer nanoscale structuring and corresponding symmetries that enable or enhance THz emission. This serves as a promising route for probing nanoscale physics and ultrafast light-matter interactions, as well as facilitating advances in integrated THz systems. Furthermore, the interplay between intrinsic and extrinsic material symmetries, in addition to hybrid structuring, may stimulate the discovery of exotic properties and phenomena beyond existing material paradigms.

11.
Mol Med Rep ; 27(4)2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36825575

RESUMO

Hereditary spastic paraplegia (HSP) comprises a group of hereditary and neurodegenerative diseases that are characterized by axonal degeneration or demyelination of bilateral corticospinal tracts in the spinal cord; affected patients exhibit progressive spasticity and weakness in the lower limbs. The most common manifestation of HSP is spastic paraplegia type 4 (SPG4), which is caused by mutations in the spastin (SPAST) gene. The present study reports the clinical characteristics of affected individuals and sequencing analysis of a mutation that caused SPG4 in a family. All affected family members exhibited spasticity and weakness of the lower limbs and, notably, only male members of the family were affected. Whole­exome sequencing revealed that all affected individuals had a novel c.1785C>A (p. Ser595Arg) missense mutation in SPAST. Bioinformatics analysis revealed changes in both secondary and tertiary structures of the mutated protein. The novel missense mutation in SPAST supported the diagnosis of SPG4 in this family and expands the spectrum of pathogenic mutations that cause SPG4. Analysis of SPAST sequences revealed that most pathogenic mutations occurred in the AAA domain of the protein, which may have a close relationship with SPG4 pathogenesis.


Assuntos
Paraplegia Espástica Hereditária , Humanos , Masculino , Paraplegia Espástica Hereditária/genética , Paraplegia Espástica Hereditária/diagnóstico , Paraplegia Espástica Hereditária/patologia , Mutação de Sentido Incorreto , Espastina/genética , Mutação
12.
ACS Appl Mater Interfaces ; 15(9): 12560-12569, 2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36847242

RESUMO

Tunable terahertz (THz) photonic devices are imperative in a wide range of applications ranging from THz signal modulation to molecular sensing. One of the currently prevailing methods is based on arrays of metallic or dielectric resonators integrated with functional materials in response to an external stimulus, in which for the purpose of sensing the external stimuli may introduce inadvertent undesirable effects into the target samples to be measured. Here we developed an alternative approach by postprocessing nanothickness macro-assembled graphene (nMAG) films with widely tunable THz conductivity, enabling versatile solid-state THz devices and sensors, showing multifunctional nMAG-based applications. The THz conductivities of free-standing nMAGs showed a broad range from 1.2 × 103 S/m in reduced graphene oxide before annealing to 4.0 × 106 S/m in a nMAG film annealed at 2800 °C. We fabricated nMAG/dielectric/metal and nMAG/dielectric/nMAG THz Salisbury absorbers with broad reflectance ranging from 0% to 80%. The highly conductive nMAG films enabled THz metasurfaces for sensing applications. Taking advantage of the resonant field enhancement arising from the plasmonic metasurface structures and the strong interactions between analyte molecules and nMAG films, we successfully detected diphenylamine with a limit of detection of 4.2 pg. Those wafer-scale nMAG films present promising potential in high-performance THz electronics, photonics, and sensors.

13.
Methods ; 208: 66-74, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36377123

RESUMO

BACKGROUND: Single cell sequencing is a technology for high-throughput sequencing analysis of genome, transcriptome and epigenome at the single cell level. It can improve the shortcomings of traditional methods, reveal the gene structure and gene expression state of a single cell, and reflect the heterogeneity between cells. Among them, the clustering analysis of single-cell RNA data is a very important step, but the clustering of single-cell RNA data is faced with two difficulties, dropout events and dimension curse. At present, many methods are only driven by data, and do not make full use of the existing biological information. RESULTS: In this work, we propose scSSA, a clustering model based on semi-supervised autoencoder, fast independent component analysis (FastICA) and Gaussian mixture clustering. Firstly, the semi-supervised autoencoder imputes and denoises the scRNA-seq data, and then get the low-dimensional latent representation. Secondly, the low-dimensional representation is reduced the dimension and clustered by FastICA and Gaussian mixture model respectively. Finally, scSSA is compared with Seurat, CIDR and other methods on 10 public scRNA-seq datasets. CONCLUSION: The results show that scSSA has superior performance in cell clustering on 10 public datasets. In conclusion, scSSA can accurately identify the cell types and is generally applicable to all kinds of single cell datasets. scSSA has great application potential in the field of scRNA-seq data analysis. Details in the code have been uploaded to the website https://github.com/houtongshuai123/scSSA/.


Assuntos
Perfilação da Expressão Gênica , Análise de Célula Única , Análise de Sequência de RNA/métodos , RNA-Seq , Análise de Célula Única/métodos , Perfilação da Expressão Gênica/métodos , Análise por Conglomerados , RNA
14.
Anal Chem ; 94(29): 10524-10530, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35822933

RESUMO

In this work, an intelligent multiregion linear DNA walker (MLDW) with a high walking rate and a high amplification efficiency was explored for ultrasensitive detection of miRNA. Significantly, amounts of functional domain could be concentrated in a long linear DNA obtained by the target miRNA-mediated rolling-circle amplification to simultaneously increase the local concentration and collision probability, resulting in an obviously improved reaction rate. Impressively, the MLDW can accomplish the reaction within 30 min, which is at least 4 times beyond that of traditional single-leg and multiple-leg DNA walkers. As a proof of concept, the high-efficiency MLDW was used to develop an electrochemical biosensing platform for ultrasensitive detection of target miRNA-21 with a low detection limit down to 36 aM. Therefore, the MLDW we designed puts forward an innovative insight to construct a functional DNA nanodevice and promote the investigation of the inherent performance of nucleic acid signal amplification for ultimate application in the detection of biomolecules and clinical disease diagnosis.


Assuntos
Técnicas Biossensoriais , MicroRNAs , Técnicas Biossensoriais/métodos , DNA/química , Técnicas Eletroquímicas/métodos , Limite de Detecção , MicroRNAs/genética , Técnicas de Amplificação de Ácido Nucleico/métodos
15.
Sci Rep ; 12(1): 3320, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35228628

RESUMO

Carbonatites host some unique ore deposits, especially REE, and fractional crystallization might be a potentially powerful mechanism for control enrichment of carbonatitic magmas by these metals to economically significant levels. At present, data on distribution coefficients of REE during fractional crystallization of carbonatitic melts at volcanic conditions are extremely scarce. Here we present an experimental study of REE partitioning between carbonatitic melts and calcite in the system CaCO3-Na2CO3 with varying amounts of P2O5, F, Cl, SiO2, SO3 at 650-900 °C and 100 MPa using cold-seal pressure vessels and LA-ICP-MS. The presence of phosphorus in the system generally increases the distribution coefficients but its effect decreases with increasing concentration. The temperature factor is high: at 770-900 °C DREE ≥ 1, while at lower temperatures DREE become below unity. Silicon also promotes the fractionation of REE into calcite, while sulfur contributes to retention of REE in the melt. Our results imply that calcite may impose significant control upon REE fractionation at the early stages of crystallization of carbonatitic magmas and might be a closest proxy for monitoring the REE content in initial melt.

16.
Nanoscale Horiz ; 7(3): 267-275, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-34908075

RESUMO

Developments in the field of nanoplasmonics have the potential to advance applications from information processing and telecommunications to light-based sensing. Traditionally, nanoscale noble metals such as gold and silver have been used to achieve the targeted enhancements in light-matter interactions that result from the presence of localized surface plasmons (LSPs). However, interest has recently shifted to intrinsically doped semiconductor nanocrystals (NCs) for their ability to display LSP resonances (LSPRs) over a much broader spectral range, including the infrared (IR). Among semiconducting plasmonic NCs, spinel metal oxides (sp-MOs) are an emerging class of materials with distinct advantages in accessing the telecommunications bands in the IR and affording useful environmental stability. Here, we report the plasmonic properties of Fe3O4 sp-MO NCs, known previously only for their magnetic functionality, and demonstrate their ability to modify the light-emission properties of telecom-emitting quantum dots (QDs). We establish the synthetic conditions for tuning sp-MO NC size, composition and doping characteristics, resulting in unprecedented tunability of electronic behavior and plasmonic response over 450 nm. In particular, with diameter-dependent variations in free-electron concentration across the Fe3O4 NC series, we introduce a strong NC size dependency onto the optical response. In addition, our observation of plasmonics-enhanced decay rates from telecom-emitting QDs reveals Purcell enhancement factors for simple plasmonic-spacer-emitter sandwich structures up to 51-fold, which are comparable to values achieved previously only for emitters in the visible range coupled with conventional noble metal NCs.

17.
Front Pharmacol ; 12: 730579, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35280253

RESUMO

Rheumatoid arthritis (RA) is a chronic autoimmune disease that is primarily characterized by synovial inflammation. Our previous studies demonstrated that the lymphatic system is critical for the development and maintenance of RA disease, and sufficient lymph drainage helps to improve joint inflammation. In this study, we found that NG-R1, the main active component in the traditional Chinese medicinal herb Sanchi, activating lymphatic function can attenuate synovial inflammation. According to histopathological staining of ankle sections, NG-R1 significantly decreased the area of inflammation and reduced bone destruction of ankle joints in TNF-Tg mice. Near infrared-indocyanine green (NIR-ICG) lymphatic imaging system has shown that NG-R1 significantly improved the lymphatic drainage function. However, the molecular mechanism of its activity is not properly understood. Our in-depth study demonstrates that NG-R1 reduced the inflammatory cytokine production of lymphatic endothelial cells (LECs) stimulated by TNF-α, and the mechanism ameliorated the phosphorylation of IKKα/ß and p65, and the translocation of p65 into the nucleus. In summary, this study proved that NG-R1 promoted lymphatic drainage function to ameliorating rheumatoid arthritis in TNF-Tg mice by suppressing NF-κB signaling pathway.

18.
Acta Biomater ; 121: 541-553, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33227489

RESUMO

Rheumatoid arthritis (RA) is a chronicautoimmune disease, marked by joint swelling and pain, articular synovial hyperplasia, as well as cartilage and bone destruction. Triptolide (TP) is an anti-inflammatory molecule but its use to treat RA is limited due to poor solubility and extremely high toxicity. In this study, by encapsulating TP into a star-shaped amphiphilic block copolymer, POSS-PCL-b-PDMAEMA, we engineered a pH-sensitive TP-loaded nanomedicine (TP@NPs) to simultaneously reduce the toxicity of TP and improve its therapeutic efficacy. TP@NPs shows a uniform spherical structure with a hydrodynamic diameter of ~92 nm and notable pH-responsiveness. In vitro TP@NPs showed reduced cytotoxicity and cell apoptosis of treated RAW264.7 cells compared to free TP. And in vivo intravenous injection of indocyanine green-labeled NPs into a collagen-induced arthritis model in mice showed that the engineered compound had potent pharmacokinetic and pharmacodynamic profiles, while exhibiting significant cartilage-protective and anti-inflammatory effects with a better efficacy and neglible systemic toxicity even at an ultralow dose compared to free TP. These results suggest that TP@NPs may be a safe and effective therapy for RA and other autoimmune diseases.


Assuntos
Artrite Reumatoide , Fenantrenos , Animais , Artrite Reumatoide/tratamento farmacológico , Diterpenos , Compostos de Epóxi , Concentração de Íons de Hidrogênio , Camundongos , Nanomedicina , Fenantrenos/farmacologia
19.
J Musculoskelet Neuronal Interact ; 20(4): 526-534, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33265080

RESUMO

OBJECTIVE: The lymphatic system plays an important role in joint diseases. This study aimed to evaluate the effects of ginsenoside Rg1 on lymphatic drainage and accumulation of inflammatory products in the joints. METHODS: Two-month-old transgenic mice that overexpress tumor necrosis factor alpha (TNF-α; TNF-Tg) were used as the animal models. Ginsenoside Rg1 was administered for 12 weeks and the lymphatic drainage in the mice was evaluated using near infrared-indocyanine green (NIR-ICG) lymphatic imaging system. The clinical symptoms of arthritis were evaluated weekly. The ankle and knee joints were harvested for hematoxylin-eosin (HE), alcian blue/orange G (ABOG), and tartrate-resistant acid phosphatase (TRAP) staining, and the foot dorsal skin was used for whole-mount immuno-staining. Simultaneously, the serum levels of IL-6 and TNF-α were detected using enzyme-linked immunosorbent assay (ELISA). RESULTS: Ginsenoside Rg1 significantly improved the lymphatic drainage function, reduced synovial inflammation and bone erosion, decreased serum IL-6 and TNF-α concentration, and increased smooth muscle coverage on the collecting lymphatic vessels in the foot skin of the TNF-Tg mice. Furthermore, ginsenoside Rg1 treatment for 12 weeks did not cause any damage to the liver and kidney tissues. CONCLUSION: Ginsenoside Rg1 improves lymphatic drainage and joint inflammation in TNF-Tg mice. Therefore, ginsenoside Rg1 has the potential to be a candidate drug for the treatment of inflammatory arthritis.


Assuntos
Artrite Experimental/patologia , Ginsenosídeos/farmacologia , Vasos Linfáticos/efeitos dos fármacos , Animais , Artrite Psoriásica/patologia , Artrite Reumatoide/patologia , Camundongos , Camundongos Transgênicos , Espondilite Anquilosante/patologia
20.
ACS Appl Mater Interfaces ; 12(20): 23076-23083, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32340437

RESUMO

Tetragonal tungsten bronze (TTB) materials are one of the most promising classes of materials for ferroelectric and nonlinear optical devices, owing to their very unique noncentrosymmetric crystal structure. In this work, a new TTB phase of LiNb6Ba5Ti4O30 (LNBTO) has been discovered and studied. A small amount of a secondary phase, LiTiO2 (LTO), has been incorporated as nanopillars that are vertically embedded in the LNBTO matrix. The new multifunctional nanocomposite thin film presents exotic highly anisotropic microstructure and properties, e.g., strong ferroelectricity, high optical transparency, anisotropic dielectric function, and strong optical nonlinearity evidenced by the second harmonic generation results. An optical waveguide structure based on the stacks of α-Si on SiO2/LNBTO-LTO has been fabricated, exhibiting low optical dispersion with an optimized evanescent field staying in the LNBTO-LTO active layer. This work highlights the combination of new TTB material designs and vertically aligned nanocomposite structures for further enhanced anisotropic and nonlinear properties.

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