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1.
Mitochondrial DNA B Resour ; 9(9): 1162-1165, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39234583

RESUMO

Dipterocarpus retusus Blume is an endangered species on the IUCN Red List. In this study, we reported the complete chloroplast (cp) genome of D. retusus (GenBank accession number: OP271853). The cp genome was 154,303 bp long, with a large single-copy (LSC) region of 85,586 bp and a small single-copy (SSC) region of 20,273 bp separated by a pair of inverted repeats (IRs) of 24,222 bp. It encodes 128 genes, including 84 protein-coding genes, 36 tRNA genes, and eight ribosomal RNA genes. We also reconstructed the cp genome phylogeny of Dipterocarpus, which indicated D. retusus was closely related with the sympatric species D. gracilis. This study may contribute valuable information to the phylogenetic relationships within the genus Dipterocarpus.

2.
Materials (Basel) ; 17(15)2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39124402

RESUMO

In the paper, the eccentric compression behavior of the truss-reinforced cross-shaped concrete-filled steel tubular (CCFST) column is investigated. A total of eighteen CCFST columns were tested under eccentric compression, and the key test variables included the reinforced truss node spacing (s = 140 mm and 200 mm), slenderness ratio (λ = 9.2, 16.6, and 23.1), and eccentricity ratio (η = 0, 0.08, and 0.15). The failure mode, deformation characteristic, stress distribution, strain distribution at the mid-span of the steel tube, and the eccentric compression bearing capacity were assessed. The results show that due to the addition of reinforced truss, the steel plates near the mid-span of eccentrically compressed CCFST columns experienced multi-wave buckling rather than single-wave buckling after the peak load was reduced to 85%, and the failure mode of concrete also changed from single-section to multi-section collapse failure. Comparisons were made with the unstiffened specimen. The ductility coefficient of the stiffened specimen with eccentricity ratios of 0.08-0.15 and node spacings of 140 mm~200 mm increased by 70~83%, approaching that of the multi-cell specimens with an increasing steel ratio of 1.8%. In addition, by comparing the test results with the calculation results of four domestic and international design codes, it was found that the Chinese codes CECS159-2018 and GB50936-2014, and the Eurocode 4 (2004) can be better employed to predict the compression bearing capacity of truss-reinforced CCFST columns.

3.
Phys Rev Lett ; 133(6): 060801, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39178437

RESUMO

Bosonic loss estimation has an important role in quantum metrology. It was once believed that the ultimate precision of this task is restricted to the standard quantum limit if no quantum probe is involved. Nevertheless, a recent proposal showed that this limit can be surpassed by utilizing ring resonators with coherent state probe. Here, we experimentally realize the resonator-based bosonic loss estimation and verify the resonant enhancement effect. This Letter explores the advantages of resonator-based metrology and sheds light on the development of high-precision miniature sensors.

4.
Langmuir ; 40(32): 16846-16854, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39094224

RESUMO

Films of the discotic liquid crystalline hexabenzocoronene (HBC) derivative, HBC-1,3,5-Ph-C12, were prepared on the quartz substrate by the bar-coating method. Depending on the coating speed, regularly spaced stripes or continuous films were observed. In the former case, columns of the HBC derivatives align more along the stripes, which are perpendicular to the coating direction, whereas in the latter case, columns of the HBC derivatives in the film align more along the coating direction. These distinctive structures are confirmed via polarized optical microscopy (POM), polarized UV-vis spectroscopy, and grazing incidence small-angle X-ray scattering measurements.

5.
Eur Spine J ; 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39168893

RESUMO

PURPOSE: Current research suggests that oxidative stress may decrease bone mineral density (BMD) by disrupting bone metabolism balance. However, no study investigated the relationship between systemic oxidative stress status and adult BMD. This study aims to investigate whether oxidative balance score (OBS) is associated with BMD in adults under 40. METHODS: 3963 participants were selected from the National Health and Nutrition Survey (NHANES) from 2011 to 2018. OBS is scored based on 20 dietary and lifestyle factors. Weighted multiple logistic regression and restricted cubic splines were used to assess the correlation between OBS and osteopenia. RESULTS: After adjusting for confounding factors, the weighted logistic regression results showed that compared with the first tertile of OBS, the highest tertile had a 38% (OR: 0.62, 95% CI: 0.47-0.82) lower risk of osteopenia. The restrictive cubic spline curve indicates a significant nonlinear correlation between OBS and the risk of osteopenia. CONCLUSION: The research findings emphasize the relationship between OBS and the risk of osteopenia in young adults. Adopting an antioxidant diet and lifestyle may help young adults to maintain bone mass.

6.
Physiol Rep ; 12(15): e16179, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39107084

RESUMO

Diabetic kidney disease (DKD) is a devastating kidney disease and lacks effective therapeutic interventions. The present study was aimed to determine whether reconstituted high-density lipoprotein (rHDL) ameliorated renal injury in eNOS-/- dbdb mice, a mouse model of DKD. Three groups of mice, wild type C57BLKS/J (non-diabetes), eNOS-/- dbdb (diabetes), and eNOS-/- dbdb treated with rHDL (diabetes+rHDL) with both males and females were used. The rHDL nanoparticles were administered to eNOS-/- dbdb mice at Week 16 at 5 µg/g body weight in ~100 µL of saline solution twice per week for 4 weeks via retroorbital injection. We found that rHDL treatment significantly blunted progression of albuminuria and GFR decline observed in DKD mice. Histological examinations showed that the rHDLs significantly alleviated glomerular injury and renal fibrosis, and inhibited podocyte loss. Western blots and immunohistochemical examinations showed that increased protein abundances of fibronectin and collagen IV in the renal cortex of eNOS-/- dbdb mice were significantly reduced by the rHDLs. Taken together, the present study suggests a renoprotective effect of rHDLs on DKD.


Assuntos
Nefropatias Diabéticas , Lipoproteínas HDL , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo III , Animais , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/patologia , Camundongos , Masculino , Óxido Nítrico Sintase Tipo III/metabolismo , Lipoproteínas HDL/farmacologia , Feminino , Camundongos Knockout , Rim/patologia , Rim/metabolismo , Rim/efeitos dos fármacos , Albuminúria , Fibronectinas/metabolismo , Fibronectinas/genética , Fibrose , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico
7.
Phytochemistry ; 228: 114259, 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39186996

RESUMO

A comprehensive phytochemical investigation of the flower buds and leaves/twigs of Heptacodium miconioides, a cultivated ornamental plant native to China and categorized as 'vulnerable', has led to the isolation of 45 structurally diverse compounds, which comprise 18 phenylpropanoids (1-4, 7-20), 11 pentacyclic triterpenoids (5, 6, 21-29), eight secoiridoid glycosides (30-37), three quinic acid derivatives (38-40), and a few miscellaneous components (41-45). Among them, (+)-α-intermedianol (1), (+)-holophyllol A (2), and (-)-pseudolarkaemin A (3) represent previously unreported enantiomeric lignans, while (+)-7'(R)-hydroxymatairesinol (4) is an undescribed naturally occurring lignan. Heptacoacids A (5) and B (6) are undescribed 24-nor-urs-28-oic acid derivatives. Their chemical structures were determined by 2D-NMR, supplemented by evidence from specific rotations and circular dichroism spectra. Given the uncertainty surrounding the systematic position of Heptacodium, integrative taxonomy (ITA), a method utilized to define contentious species, is applied. Chemotaxonomy, a vital aspect of ITA, becomes significant. By employing hierarchical clustering analysis (HCA) and syntenic pattern analysis methods, a taxonomic examination based on the major specialized natural products from the flower buds of H. miconioides and two other Caprifoliaceae plants (i.e., Lonicera japonica and Abelia × grandiflora) could offer enhanced understanding of the systematic placement of Heptacodium. Additionally, compounds 39 and 40 displayed remarkable inhibitory activities against ATP-citrate lyase (ACL), with IC50 values of 0.11 and 1.10 µM, respectively. In summary, the discovery of medical properties and refining systematic classification can establish a sturdy groundwork for conservation efforts aimed at mitigating species diversity loss while addressing human diseases.

8.
Environ Res ; 262(Pt 1): 119792, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39142455

RESUMO

The functionality of activated sludge in wastewater treatment processes depends largely on the structural and microbial composition of its flocs, which are complex assemblages of microorganisms and their secretions. However, monitoring these flocs in real-time and consistently has been challenging due to the lack of suitable technologies and analytical methods. Here we present a laboratory setup capable of capturing instantaneous microscopic images of activated sludge, along with algorithms to interpret these images. To improve floc identification, an advanced Mask R-CNN-based segmentation that integrates a Dual Attention Network (DANet) with an enhanced Feature Pyramid Network (FPN) was used to enhance feature extraction and segmentation accuracy. Additionally, our novel PointRend module meticulously refines the contours of boundaries, significantly minimising pixel inaccuracies. Impressively, our approach achieved a floc detection accuracy of >95%. This development marks a significant advancement in real-time sludge monitoring, offering essential insights for optimising wastewater treatment operations proactively.

9.
BMC Psychiatry ; 24(1): 583, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39192231

RESUMO

BACKGROUND: This study was intended to investigate the correlation between depression and suicidal ideation among Chinese college students during the COVID-19 pandemic and the potential mediating roles of chronotype and sleep quality in this relationship . METHODS: A sample of 4,768 college students was selected from four institutions in Anhui Province, China, and the study was conducted during the COVID-19 pandemic (November to December 2020) using a stratified, cluster, multi-stage sampling method. This study used the two-item Patient Health Questionnaire (PHQ-2) to assess depressive symptoms, the Morningness-Eveningness Questionnaire 19 (MEQ-19) to determine individual sleep chronotypes (i.e., morning or evening preference), and the Pittsburgh Sleep Quality Index (PSQI) to evaluate sleep quality. Participants were asked about suicidal ideation. MPLUS 8.3 software was used to analyze the mediating effect of chronotype and sleep quality on the relationship between depression and suicidal ideation. RESULTS: During the COVID-19 pandemic, the prevalence of suicidal ideation among Chinese college students was 5.4%. Depression was inversely correlated with chronotype (beta = - 0.346, P < 0.01) and positively correlated with sleep quality (beta = 0.846, P < 0.001), indicating that students experiencing depressive symptoms were more likely to have a later chronotype and poor sleep quality. A later chronotype (beta = - 0.019, P < 0.05) and poor sleep quality (beta = 0.066, P < 0.01) predicted suicidal ideation. Depression emerged as a direct and significant risk factor for suicidal ideation (effect value = 0.535, 95% confidence interval: 0.449 ~ 0.622). Chronotype and sleep quality were found to have potential mediating effects on the relationship between depression and suicidal ideation; however, the chain-mediating effect of chronotype and sleep quality was not statistically significant. CONCLUSIONS: Our findings suggest that during the COVID-19 pandemic, depression can precipitate suicidal ideation through its influence on sleep chronotype and quality. These compelling findings highlight the urgency of early intervention strategies intended to mitigate suicidal thoughts, particularly among students exhibiting depressive symptoms, who experience disrupted sleep patterns and poor sleep quality.


Assuntos
COVID-19 , Depressão , Qualidade do Sono , Estudantes , Ideação Suicida , Humanos , COVID-19/psicologia , COVID-19/epidemiologia , Estudantes/psicologia , Feminino , Masculino , China/epidemiologia , Depressão/psicologia , Depressão/epidemiologia , Adulto Jovem , Universidades , Adulto , Adolescente , Ritmo Circadiano/fisiologia , Inquéritos e Questionários , Prevalência , Cronotipo
10.
ACS Appl Mater Interfaces ; 16(31): 41518-41533, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39046307

RESUMO

Dental caries, one of the most prevalent infectious diseases, is the primary contributor to the early loss of natural teeth and is a significant public health issue. Known as the tooth's bioactive core, the dentin-pulp complex (DPCX) comprises tightly connected hard and soft tissues that not only serve as a biological barrier for the inner tooth tissue but also produce reparative dentin following mild disruptions. While efforts to preserve DPCX are numerous, most strategies focus on temporary antibacterial measures, inflammation reduction, or tissue regeneration, lacking a comprehensive, long-lasting solution. In this study, TVH-19, an autoadaptive peptide mimicking the pH- and ion-responsive capacity of amelogenin, was designed to exert multifaceted preservation of DPCX, providing a comprehensive strategy for preserving vital pulp. Leveraging its unique amphiphilicity-related cell penetration and ion/pH-responsive self-assembly properties, TVH-19 outperforms conventional pulp preservation materials by being capable of rapid cell penetration, minimizing diffused side effects, providing environment-responsive self-assembly/disassembly for balanced long-term antibacterial and cell protection, and facilitating the formation of lysosomal-escaping intracellular aggregates for the continuous activation of PDGFRα+ dental pulp stem cells.


Assuntos
Amelogenina , Cárie Dentária , Polpa Dentária , Dentina , Polpa Dentária/efeitos dos fármacos , Cárie Dentária/prevenção & controle , Dentina/química , Dentina/efeitos dos fármacos , Amelogenina/química , Animais , Humanos , Peptídeos/química , Peptídeos/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Concentração de Íons de Hidrogênio , Camundongos
11.
Int J Biol Macromol ; 276(Pt 1): 133647, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38964693

RESUMO

Teeth discoloration poses a widespread challenge in dental health across various regions. Conventional teeth whitening methods often result in enamel deterioration and soft tissue harm due to the utilization of incompatible whitening agents and continuous intense light exposure. Here, we propose an effective phototherapy technique for teeth whitening, employing pathways of energy transition through intersystem crossing. The integration of MoS2 nanosheets into carrageenan gel (MoS2 NSs@Carr) facilitates both photothermal-hyperthermia and the generation of reactive oxygen species (ROS) through photocatalytic processes. The efficacy of ROS generation by the phototherapeutic MoS2 NSs@Carr on teeth whitening in the scenario. This approach ensures comprehensive teeth whitening by eliminating deep-seated stains on the teeth while preserving structural integrity and avoiding any tissue toxicity. This research highlights the efficacy of the phototherapeutic MoS2 NSs@Carr for dental whitening and underscores the potential of exploring nanostructures based on MoS2 NSs for managing dental healthcare issue.


Assuntos
Carragenina , Dissulfetos , Hidrogéis , Molibdênio , Clareamento Dental , Molibdênio/química , Dissulfetos/química , Clareamento Dental/métodos , Hidrogéis/química , Carragenina/química , Humanos , Espécies Reativas de Oxigênio/metabolismo , Animais , Assistência Odontológica , Fototerapia/métodos , Nanoestruturas/química
12.
Opt Lett ; 49(14): 3982-3985, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39008758

RESUMO

Ultraviolet and color imaging require different image sensors and optical channels, which results in large size, complex structure, and high cost of imaging systems. Here, we report a novel, to the best of our knowledge, image sensor that combines ultraviolet and color imaging functions. The fabrication of this image sensor is achieved by coating high-transparency CsPbBr3 perovskite nanocrystals in a polymer film on the color filter layer of a silicon-based detector. The film, serving as an ultraviolet photoluminescent layer, exhibits high transparency, exceeding 91.5% at wavelengths beyond the photoluminescence peak of 513 nm. During ultraviolet imaging, the film converts ultraviolet light into visible light, which passes through the green filter layer to reach the detector for imaging. During visible light imaging, red light, green light, and most of the blue light pass through the CsPbBr3 perovskite nanocrystal film and color filter layer to reach the detector for imaging. As a result, the image sensor can capture both 257 nm solar-blind ultraviolet images and color photos in the visible light.

13.
Apoptosis ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39044092

RESUMO

Homocysteine (Hcy) is a metabolic intermediate product derived from methionine. Hyperhomocysteinemia is a condition associated with various diseases. Hcy is recognized as a risk factor for cardiovascular disease (CVD). Ferroptosis, a novel form of cell death, is primarily characterized by substantial iron accumulation and lipid peroxidation. Recent research indicates a close association between ferroptosis and the pathophysiological processes of tumors, neurological diseases, CVD, and other ailments. However, limited research has been conducted on the impact of Hcy on ferroptosis. Therefore, this paper aimed to investigate the potential roles and mechanisms of homocysteine and ferroptosis in the context of cardiovascular disease. By conducting comprehensive literature research and analysis, we aimed to summarize recent advancements in understanding the effects of homocysteine on ferroptosis in cardiovascular diseases. This research contributes to a profound understanding of this critical domain.

14.
Planta ; 260(2): 50, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990341

RESUMO

MAIN CONCLUSION: BcERF98 is induced by ethylene signaling and inhibits the expression of BcFT by interacting with BcNF-YA2 and BcEIP9, thereby inhibiting plant flowering. Several stresses trigger the accumulation of ethylene, which then transmits the signal to ethylene response factors (ERFs) to participate in the regulation of plant development to adapt to the environment. This study clarifies the function of BcERF98, a homolog of AtERF98, in the regulation of plant flowering time mediated by high concentrations of ethylene. Results indicate that BcERF98 is a nuclear and the cell membrane-localized transcription factor and highly responsive to ethylene signaling. BcERF98 inhibits the expression of BcFT by interacting with BcEIP9 and BcNF-YA2, which are related to flowering time regulation, thereby participating in ethylene-mediated plant late flowering regulation. The results have enriched the theoretical knowledge of flowering regulation in non-heading Chinese cabbage (NHCC), providing the scientific basis and gene reserves for cultivating new varieties of NHCC with different flowering times.


Assuntos
Etilenos , Flores , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Fatores de Transcrição , Flores/genética , Flores/fisiologia , Flores/crescimento & desenvolvimento , Etilenos/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Brassica/genética , Brassica/fisiologia , Brassica/metabolismo , Brassica/crescimento & desenvolvimento , Transdução de Sinais , Reguladores de Crescimento de Plantas/metabolismo
15.
Saudi Pharm J ; 32(7): 102124, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38933713

RESUMO

Natural products (NPs) play an irreplaceable role in the intervention of various diseases and have been considered a critical source of drug development. Many new pharmacodynamic compounds with potential clinical applications have recently been derived from NPs. These compounds range from small molecules to polysaccharides, polypeptides, proteins, self-assembled nanoparticles, and extracellular vesicles. This review summarizes various active substances found in NPs. The investigation of active substances in NPs can potentiate new drug development and promote the in-depth comprehension of the mechanism of action of NPs that can be beneficial in the prevention and treatment of human diseases.

16.
Nat Commun ; 15(1): 5469, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937477

RESUMO

Porous frameworks constructed via noncovalent interactions show wide potential in molecular separation and gas adsorption. However, it remains a major challenge to prepare these materials from low-symmetry molecular building blocks. Herein, we report a facile strategy to fabricate noncovalent porous crystals through modular self-assembly of a low-symmetry helicene racemate. The P and M enantiomers in the racemate first stack into right- and left-handed triangular prisms, respectively, and subsequently the two types of prisms alternatively stack together into a hexagonal network with one-dimensional channels with a diameter of 14.5 Å. Remarkably, the framework reveals high stability upon heating to 275 °C, majorly due to the abundant π-interactions between the complementarily engaged helicene building blocks. Such porous framework can be readily prepared by fast rotary evaporation, and is easy to recycle and repeatedly reform. The refined porous structure and enriched π-conjugation also favor the selective adsorption of a series of small molecules.

17.
NPJ Biofilms Microbiomes ; 10(1): 51, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902226

RESUMO

Bacteria induced metamorphosis observed in nearly all marine invertebrates. However, the mechanism of bacteria regulating the larvae-juvenile metamorphosis remains unknown. Here, we test the hypothesis that c-di-GMP, a ubiquitous bacterial second-messenger molecule, directly triggers the mollusc Mytilus coruscus larval metamorphosis via the stimulator of interferon genes (STING) receptor. We determined that the deletion of c-di-GMP synthesis genes resulted in reduced c-di-GMP levels and biofilm-inducing activity on larval metamorphosis, accompanied by alterations in extracellular polymeric substances. Additionally, c-di-GMP extracted from tested varying marine bacteria all exhibited inducing activity on larval metamorphosis. Simultaneously, through pharmacological and molecular experiments, we demonstrated that M. coruscus STING (McSTING) participates in larval metamorphosis by binding with c-di-GMP. Our findings reveal that new role of bacterial c-di-GMP that triggers mussel larval metamorphosis transition, and extend knowledge in the interaction of bacteria and host development in marine ecosystems.


Assuntos
Biofilmes , GMP Cíclico , Larva , Metamorfose Biológica , Mytilus , Animais , Larva/microbiologia , Larva/crescimento & desenvolvimento , GMP Cíclico/análogos & derivados , GMP Cíclico/metabolismo , Biofilmes/crescimento & desenvolvimento , Mytilus/microbiologia , Mytilus/crescimento & desenvolvimento , Bactérias/genética , Bactérias/classificação , Bactérias/metabolismo , Bactérias/crescimento & desenvolvimento , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo
19.
Biomaterials ; 311: 122645, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38850717

RESUMO

Immunotherapy through the activation of the stimulator of interferon genes (STING) signaling pathway is increasingly recognized for its robust anti-tumor efficacy. However, the effectiveness of STING activation is often compromised by inadequate anti-tumor immunity and a scarcity of primed immune cells in the tumor microenvironment. Herein, we design and fabricate a co-axial 3D-printed scaffold integrating a non-nucleotide STING agonist, SR-717, and an AKT inhibitor, MK-2206, in its respective shell and core layers, to synergistically enhance STING activation, thereby suppressing tumor recurrence and growth. SR-717 initiates the STING activation to enhance the phosphorylation of the factors along the STING pathway, while MK-2206 concurrently inhibits the AKT phosphorylation to facilitate the TBK1 phosphorylation of the STING pathway. The sequential and sustained release of SR-717 and MK-2206 from the scaffold results in a synergistic STING activation, demonstrating substantial anti-tumor efficacy across multiple tumor models. Furthermore, the scaffold promotes the recruitment and enrichment of activated dendritic cells and M1 macrophages, subsequently stimulating anti-tumor T cell activity, thereby amplifying the immunotherapeutic effect. This precise and synergistic activation of STING by the scaffold offers promising potential in tumor immunotherapy.


Assuntos
Compostos Heterocíclicos com 3 Anéis , Imunoterapia , Proteínas de Membrana , Impressão Tridimensional , Proteínas Proto-Oncogênicas c-akt , Animais , Proteínas de Membrana/agonistas , Proteínas de Membrana/metabolismo , Imunoterapia/métodos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Compostos Heterocíclicos com 3 Anéis/farmacologia , Camundongos , Alicerces Teciduais/química , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Humanos , Feminino , Camundongos Endogâmicos BALB C
20.
Adv Sci (Weinh) ; 11(31): e2309940, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38874114

RESUMO

Liver fibrosis is a chronic pathological condition lacking specific clinical treatments. Stem cells, with notable potential in regenerative medicine, offer promise in treating liver fibrosis. However, stem cell therapy is hindered by potential immunological rejection, carcinogenesis risk, efficacy variation, and high cost. Stem cell secretome-based cell-free therapy offers potential solutions to address these challenges, but it is limited by low delivery efficiency and rapid clearance. Herein, an innovative approach for in situ implantation of smart microneedle (MN) arrays enabling precisely controlled delivery of multiple therapeutic agents directly into fibrotic liver tissues is developed. By integrating cell-free and platinum-based nanocatalytic combination therapy, the MN arrays can deactivate hepatic stellate cells. Moreover, they promote excessive extracellular matrix degradation by more than 75%, approaching normal levels. Additionally, the smart MN arrays can provide hepatocyte protection while reducing inflammation levels by ≈70-90%. They can also exhibit remarkable capability in scavenging almost 100% of reactive oxygen species and alleviating hypoxia. Ultimately, this treatment strategy can effectively restrain fibrosis progression. The comprehensive in vitro and in vivo experiments, supplemented by proteome and transcriptome analyses, substantiate the effectiveness of the approach in treating liver fibrosis, holding immense promise for clinical applications.


Assuntos
Cirrose Hepática , Agulhas , Animais , Cirrose Hepática/terapia , Camundongos , Modelos Animais de Doenças , Humanos , Masculino , Sistema Livre de Células
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