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Cellular communication mediated by messenger molecules plays an important role in the progression of cancer. Herein, pH-sensitive zeolitic imidazolate framework-8 (ZIF-8) loaded with PtCl2(OH)2(NH3)2 [i.e., Pt(IV)] bimetallic nanoplatforms were developed for prostate cancer therapy by interfering inositol-1, 4, 5-trisphosphate (IP3)-mediated cellular communication. As an important messenger in cells, the function of IP3 was found to be efficiently interfered with by the Pt(IV)-binding inositol unit. This finding effect of Pt(IV) is totally different from its traditional function as a prodrug of cis-platinum for chemotherapy. The decreased IP3 signal further downregulated the cytoplasmic Ca2+ concentration and downstream signal transduction to inhibit proliferation and invasion of tumor cells. Meanwhile, Zn2+ released from ZIF-8 under an acidic tumor microenvironment decreased adenosine triphosphate biosynthesis, which could further limit the cellular communication. Such a proposed strategy of interfering cellular communication has demonstrated its feasibility in this study, which may provide new perspectives for cancer therapy.
Assuntos
Antineoplásicos , Neoplasias da Próstata , Humanos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Masculino , Antineoplásicos/farmacologia , Antineoplásicos/química , Comunicação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Inositol 1,4,5-Trifosfato/metabolismo , Inositol 1,4,5-Trifosfato/química , Concentração de Íons de Hidrogênio , Imidazóis/química , Imidazóis/farmacologia , Zinco/química , Zinco/farmacologiaRESUMO
It is well-known that the bacterial microenvironment imposes restrictions on the growth and behavior of bacteria. The localized monitoring of microenvironmental factors is appreciated when consulting bacterial adaptation and behavior in the presence of chemical or mechanical stimuli. Herein, we developed a novel liquid crystal (LC) biosensor in a microsphere configuration for real-time 3D monitoring of the bacteria microenvironment, which was implemented by a microfluidic chip. As a proof of concept, a LC gel (LC-Gel) microsphere biosensor was prepared and employed in the localized pH changes of bacteria by observing the configuration change of LC under polarized optical microscopy. Briefly, the microsphere biosensor was constructed in core-shell configuration, wherein the core contained LCE7 (a nematic LC) doped with 4-pentylbiphenyl-4'-carboxylic acid (PBA), and the shell encapsulated the bacteria. The protonation of carboxyl functional groups of the PBA induced a change in charge density on the surface of LCE7 and the orientation of E7 molecules, resulting in the transitions of the LC nucleus from axial to bipolar. The developed LC-Gel microspheres pH sensor exhibited its dominant performance on localized pH real-time sensing with a resolution of 0.1. An intriguing observation from the prepared pH biosensor was that the diverse bacteria impelled distinct acidifying or alkalizing effects. Overall, the facile LC-Gel microsphere biosensor not only provides a versatile tool for label-free, localized pH monitoring but also opens avenues for investigating the effects of chemical and mechanical stimuli on cellular metabolism within bacterial microenvironments.
Assuntos
Técnicas Biossensoriais , Cristais Líquidos , Microesferas , Concentração de Íons de Hidrogênio , Cristais Líquidos/química , Escherichia coliRESUMO
BACKGROUND: YouTube, a widely recognized global video platform, is inaccessible in China, whereas Bilibili and TikTok are popular platforms for long and short videos, respectively. There are many videos related to laryngeal carcinoma on these platforms. This study aims to identify upload sources, contents, and feature information of these videos on YouTube, Bilibili, and TikTok, and further evaluate the video quality. METHODS: On January 1, 2024, we searched the top 100 videos by default sort order (300 videos in total) with the terms "laryngeal carcinoma" and "throat cancer" on YouTube, "" on Bilibili and TikTok. Videos were screened for relevance and similarity. Video characteristics were documented, and quality was assessed by using the Patient Education Materials Assessment Tool (PEMAT), Video Information and Quality Index (VIQI), Global Quality Score (GQS), and modified DISCERN (mDISCERN). RESULTS: The analysis included 99 YouTube videos, 76 from Bilibili, and 73 from TikTok. Median video lengths were 193 s (YouTube), 136 s (Bilibili), and 42 s (TikTok). TikTok videos demonstrated higher audience interaction. Bilibili had the lowest ratio of original contents (69.7%). Treatment was the most popular topic on YouTube and Bilibili, while that was the prognosis on TikTok. Solo narration was the most common video style across all platforms. Video uploaders were predominantly non-profit organizations (YouTube), self-media (Bilibili), and doctors (TikTok), with TikTok authors having the highest certification rate (83.3%). Video quality, assessed using PEMAT, VIQI, GQS, and mDISCERN, varied across platforms, with YouTube generally showing the highest scores. Videos from professional authors performed better than videos from non-professionals based on the GQS and mDISCERN scores. Spearman correlation analysis showed no strong relationships between the video quality and the audience interaction. CONCLUSIONS: Videos on social media platforms can help the public learn about the knowledge of laryngeal cancer to some extent. TikTok achieves the best flow, but videos on YouTube are of the best quality. However, the video quality across all platforms still needs enhancement. We need more professional uploaders to ameliorate the video quality related to laryngeal carcinoma. Content creators also should be aware of the certification, the originality, and the style of video shooting. As for the platforms, refining the algorithm will allow users to receive more high-quality videos.
Assuntos
Neoplasias Laríngeas , Mídias Sociais , Gravação em Vídeo , Humanos , Mídias Sociais/estatística & dados numéricos , Estudos Transversais , China , Disseminação de Informação/métodos , Informação de Saúde ao Consumidor/normasRESUMO
Wound infections, especially those caused by pathogenic bacteria, present a considerable public health concern due to associated complications and poor therapeutic outcomes. Herein, we developed antibacterial nanoparticles, namely, PGTP, by coordinating guanidine derivatives with a porphyrin-based sonosensitizer. The synthesized PGTP nanoparticles, characterized by their strong positive charge, effectively disrupted the bacterial biosynthesis process through charge interference, demonstrating efficacy against both Gram-negative and Gram-positive bacteria. Additionally, PGTP nanoparticles generated reactive oxygen species under ultrasound stimulation, resulting in the disruption of biofilm integrity and efficient elimination of pathogens. RNA-seq analysis unveiled the detailed mechanism of wound healing, revealing that PGTP nanoparticles, when coupled with ultrasound, impair bacterial metabolism by interfering with the synthesis and transcription of amino acids. This study presents a novel approach to combatting wound infections through ultrasound-driven charge-interfering therapy, facilitated by advanced antibacterial nanomaterials.
Assuntos
Antibacterianos , Biofilmes , Nanopartículas , Infecção dos Ferimentos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/uso terapêutico , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Nanopartículas/química , Nanopartículas/uso terapêutico , Biofilmes/efeitos dos fármacos , Animais , Camundongos , Ondas Ultrassônicas , Espécies Reativas de Oxigênio/metabolismo , Cicatrização/efeitos dos fármacos , Humanos , Porfirinas/química , Porfirinas/farmacologia , Porfirinas/uso terapêutico , Terapia por Ultrassom/métodos , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacosRESUMO
OBJECTIVE: The study aims to examine the involvement of lincRNA00907 in the advancement of non-alcoholic steatohepatitis (NASH). METHODS: The examination was conducted to assess the expression of linc00907 in liver tissues from NASH patients and healthy individuals. High-fat diets induced NASH in mouse models, while palmitic acid/oleic acid treatment was used to create in vitro cell models. Various techniques, such as qRT-PCR, Oil Red O staining and gene knockdown/overexpression, were used to assess the impact of linc00907 on genes related to lipid metabolism and immunity, as well as intracellular lipid accumulation. Furthermore, dual-luciferase reporter assays were carried out to confirm the connection between miRNA-942-5p and linc00907 or TAOK1 mRNA. RESULTS: Linc00907 was found to be significantly upregulated in both NASH patients and NASH mouse models. Overexpression of linc00907 led to an increase in intracellular lipid accumulation, while knockdown of linc00907 resulted in decreased lipid content. It was found that miRNA-942-5p binds with linc00907, and their interaction was confirmed in dual-luciferase reporter assays. Additionally, TAOK1 was predicted to be a downstream target of miRNA-942-5p, and the upregulation of TAOK1 due to linc00907 was reversed by miRNA-942-5p overexpression. linc00907 overexpression reduces apoptosis but can be reversed by TAOK1 knockdown. The reduction of TAOK1 counteracted the impact of linc00907 on gene expression associated with lipid metabolism and immunity, as well as on the accumulation of intracellular lipids. CONCLUSIONS: Our research suggests that linc00907 functions as a competitive endogenous RNA (ceRNA) by sequestering miRNA-942-5p, thus increasing the expression of TAOK1 and encouraging lipid accumulation in hepatocytes, leading to the aggravation of NASH development. Targeting the linc00907/miRNA-942-5p/TAOK1 axis may hold therapeutic potential for the treatment of NASH.
Assuntos
MicroRNAs , Hepatopatia Gordurosa não Alcoólica , RNA Longo não Codificante , Animais , Humanos , Masculino , Camundongos , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Progressão da Doença , Metabolismo dos Lipídeos/genética , Fígado/metabolismo , Fígado/patologia , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismoRESUMO
In order to prepare highly heat-resistant packaging insulation materials, in this paper, bismaleimide/epoxy resin (BMI/EP55) composites with different contents of BMI were prepared by melt blending BMI into amino tetrafunctional and phenolic epoxy resin (at a ratio of 5:5). The microstructures and thermal and electrical properties of the composites were tested. The electrostatic potential distribution, energy level distribution, and molecular orbitals of BMI were calculated using Gaussian. The results showed that the carbonyl group in BMI is highly electronegative, implying that the carbonyl group has a strong electron trapping ability. The thermal decomposition temperature of the composites gradually increased with the increase of BMI content, and the 20% BMI/EP55 composites had the highest heat-resistance index, along with a glass transition temperature (Tg) of >250 °C. At different test temperatures, with increase in the BMI content, the conductivity of epoxy resin composites showed a tendency to first decrease and then increase, the breakdown field strength showed a tendency to first increase and then decrease, and the dielectric constant was gradually decreased. Two trap centers were present simultaneously in the composites, where the shallow trap energy level is the deepest in 20% BMI/EP composites and the deep trap energy level is the deepest in 10% BMI/EP55 composites. Correspondingly, the 10% BMI/EP55 composite had a slower charge decay rate, while the 20% BMI/EP55 had a faster charge decay rate. In summary, the BMI/EP55 composites with high heat resistance and insulating properties were prepared in this study, which provided ideas for preparing high-temperature packaging insulating materials.
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There are many instances of hollow-structure morphogenesis in the development of tissues. Thus, the fabrication of hollow structures in a simple, high-throughput and homogeneous manner with proper natural biomaterial combination is valuable for developmental studies and tissue engineering, while it is a significant challenge in biofabrication field. We present a novel method for the fabrication of a hollow cell module using a coaxial co-flow capillary microfluidic device. Sacrificial gelatin laden with cells in the inner layer and GelMa in the outer layer are used via a coaxial co-flow capillary microfluidic device to produce homogenous micro-beads. The overall and core sizes of core-shell microbeads were well controlled. When using human vein vascular endothelial cells to demonstrate how cells line the inner surface of core-shell beads, as the core liquifies, a hollow cell ball with asymmetric features is fabricated. After release from the GelMa shell, individual cell balls are obtained and deformed cell balls can self-recover. This platform paves way for complex hollow tissue modeling in vitro, and further modulation of matrix stiffness, curvature and biochemical composition to mimic in vivo microenvironments.
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Polymethoxyflavones (PMFs) are a class of abundant specialized metabolites with remarkable anticancer properties in citrus. Multiple methoxy groups in PMFs are derived from methylation modification catalyzed by a series of hydroxylases and O-methyltransferases (OMTs). However, the specific OMTs that catalyze the systematic O-methylation of hydroxyflavones remain largely unknown. Here, we report that PMFs are highly accumulated in wild mandarins and mandarin-derived accessions, while undetectable in early-diverging citrus species and related species. Our results demonstrated that three homologous genes, CreOMT3, CreOMT4, and CreOMT5, are crucial for PMF biosynthesis in citrus, and their encoded methyltransferases exhibit multisite O-methylation activities for hydroxyflavones, producing seven PMFs in vitro and in vivo. Comparative genomic and syntenic analyses indicated that the tandem CreOMT3, CreOMT4, and CreOMT5 may be duplicated from CreOMT6 and contributes to the genetic basis of PMF biosynthesis in the mandarin group through neofunctionalization. We also demonstrated that N17 in CreOMT4 is an essential amino acid residue for C3-, C5-, C6-, and C3'-O-methylation activity and provided a rationale for the functional deficiency of OMT6 to produce PMFs in early-diverging citrus and some domesticated citrus species. A 1,041-bp deletion in the CreOMT4 promoter, which is found in most modern cultivated mandarins, has reduced the PMF content relative to that in wild and early-admixture mandarins. This study provides a framework for reconstructing PMF biosynthetic pathways, which may facilitate the breeding of citrus fruits with enhanced health benefits.
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Citrus , Citrus/química , Domesticação , Melhoramento Vegetal , Metilação , Metiltransferases/metabolismoRESUMO
Liquid crystal monomers (LCMs), identified as emerging contaminations, have been detected in soils and plants, but their accumulation characteristics in plants haven't been studied. Therefore, this study systematically investigated the accumulation characteristics of LCMs in plants from four dimensions (i.e., plant fruit species, soil types, plant growth stages, and LCMs categories) for the first time. The LCMs concentrations (9.96 × 10-4 to 114.608 ng/g) in 22 plant fruits were predicted by the partition-limited model. Grains with the highest lipid content showed the highest LCMs accumulation propensity. Plants grown in paddy soil showed a strong LCMs accumulation capacity. Results showed that the LCMs accumulation capacity in plants from soils decreased when the soil organic matter content increased. A preferential accumulation of LCMs in plant root systems during growth was found by the molecular dynamics simulations. Compared to polychlorinated biphenyls (as the reference contaminants of LCMs), LCMs exhibit higher accumulation in plant roots and lower translocation to shoots. For the fourth dimension, lipophilicity was found to be the main reason of LCMs accumulation by intergraded stepwise linear regression with sensitivity analysis. This is the inaugural research concentrating on LCMs accumulation in plants, providing insights and theoretical guidance for future LCMs management strategies multidimensionally.
Assuntos
Cristais Líquidos , Poluentes do Solo , Traqueófitas , Poluentes do Solo/análise , Plantas , Raízes de Plantas/química , Solo/químicaRESUMO
BACKGROUND: Finding a drug for early intervention in the hepatic fibrosis process has important clinical significance. Previous studies have suggested SUMOylation as a potential target for intervention in hepatic fibrosis. However, the role of SAE1, a marker of SUMOylation, in hepatic fibrosis is unknown. Additionally, whether ginkgolic acid (GA), a SUMOylation inhibitor, inhibits hepatic fibrosis by inhibiting SUMO1-activating enzyme subunit 1 (SAE1) should be further investigated. METHODS: Liver tissues of patients with hepatic cirrhosis and a rat model of hepatic fibrosis constructed with CCl4 (400 mg/kg, twice weekly) or TAA (200 mg/kg, twice weekly) were selected, and the degree of hepatic fibrosis was then evaluated using H&E, Sirius red, and Masson's trichrome staining. After knockdown or overexpression of SAE1 in hepatic stellate cells, the expression levels of ferroptosis and hepatic fibrosis markers were measured in vitro. After intervention with a ferroptosis inhibitor, the expression levels were again measured in vivo and in vitro. RESULTS: We first demonstrated that SAE1 increased in patients with hepatic cirrhosis. Subsequently, testing of the rat hepatic fibrosis model confirmed that GA reduced the expression of SAE1 and improved hepatic fibrosis in rats. Then, we used hepatic stellate cell lines to confirm in vitro that GA inhibited SAE1 expression and induced ferroptosis, and that overexpression of SAE1 or inhibition of ferroptosis reversed this process. Finally, we confirmed in vivo that GA induced ferroptosis and alleviated the progression of hepatic fibrosis, while inhibiting ferroptosis also reversed the progression of hepatic fibrosis in rats. CONCLUSION: SAE1 is a potential anti-fibrotic target protein, and GA induces ferroptosis of hepatic stellate cells by targeting SAE1 to exert an anti-hepatic fibrosis effect, which lays an experimental foundation for the future clinical application of its anti-hepatic fibrosis effect.
Assuntos
Ferroptose , Salicilatos , Humanos , Ratos , Animais , Transdução de Sinais , Cirrose Hepática/metabolismo , Fígado , Células Estreladas do Fígado , Enzimas Ativadoras de Ubiquitina/metabolismo , Enzimas Ativadoras de Ubiquitina/farmacologiaRESUMO
One of the main challenges in tissue engineering is finding a way to deliver specific growth factors (GFs) with precise spatiotemporal control over their presentation. Here, we report a novel strategy for generating microscale carriers with enhanced affinity for high content loading suitable for the sustained and localized delivery of GFs. Our developed microparticles can be injected locally and sustainably release encapsulated growth factors for up to 28 days. Fine-tuning of particles' size, affinity, microstructures, and release kinetics is achieved using a microfluidic system along with bioconjugation techniques. We also describe an innovative 3D micromixer platform to control the formation of core-shell particles based on superaffinity using a polymer-peptide conjugate for further tuning of release kinetics and delayed degradation. Chitosan shells block the burst release of encapsulated GFs and enable their sustained delivery for up to 10 days. The matched release profiles and degradation provide the local tissues with biomimetic, developmental-biologic-compatible signals to maximize regenerative effects. The versatility of this approach is verified using three different therapeutic proteins, including human bone morphogenetic protein-2 (rhBMP-2), vascular endothelial growth factor (VEGF), and stromal cell-derived factor 1 (SDF-1α). As in vivo morphogenesis is typically driven by the combined action of several growth factors, the proposed technique can be developed to generate a library of GF-loaded particles with designated release profiles.