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Traditional Chinese medicine (TCM) is increasingly recognized and utilized worldwide. However, the complex ingredients of TCM and their interactions with the human body make elucidating molecular mechanisms challenging, which greatly hinders the modernization of TCM. In 2016, we developed BATMAN-TCM 1.0, which is an integrated database of TCM ingredient-target protein interaction (TTI) for pharmacology research. Here, to address the growing need for a higher coverage TTI dataset, and using omics data to screen active TCM ingredients or herbs for complex disease treatment, we updated BATMAN-TCM to version 2.0 (http://bionet.ncpsb.org.cn/batman-tcm/). Using the same protocol as version 1.0, we collected 17 068 known TTIs by manual curation (with a 62.3-fold increase), and predicted â¼2.3 million high-confidence TTIs. In addition, we incorporated three new features into the updated version: (i) it enables simultaneous exploration of the target of TCM ingredient for pharmacology research and TCM ingredients binding to target proteins for drug discovery; (ii) it has significantly expanded TTI coverage; and (iii) the website was redesigned for better user experience and higher speed. We believe that BATMAN-TCM 2.0, as a discovery repository, will contribute to the study of TCM molecular mechanisms and the development of new drugs for complex diseases.
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Bases de Dados de Produtos Farmacêuticos , Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Farmacologia em Rede , Humanos , Medicamentos de Ervas Chinesas/química , ProteínasRESUMO
As the most advanced non-viral delivery system, lipid nanoparticles (LNPs) were approved by the FDA, propelling the advancements of gene therapy. However, their clinical applications are hampered by the potential immunogenicity of the lipid components that trigger immune-related adverse events, like inflammation and allergy. Herein, we formulate various dLNPs with diminished immunogenicity by incorporating dexamethasone (Dex) into liver-, spleen-, and lung-targeting LNPs formulations that exhibit excellent abilities to target specific organs and deliver various types of RNA, such as mRNA and siRNA. In vivo investigations demonstrate unparalleled advantages in safety compared to conventional LNPs, showing promising potential in the development of RNA therapeutics. Intriguingly, the encapsulation of runt-related transcription factor-1 siRNA (siRUNX1) into lung-targeting dLNPs (dLNPs@siRUNX1) demonstrates remarkable advantages in the treatment of pulmonary fibrosis through the synergy of gene therapy and drug therapy. This research establishes secure and universal platforms for the precise delivery of nucleic acid therapeutics, showcasing promising clinical applications in gene therapy.
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Insufficient accumulation of lipid nanoparticles (LNPs)-based mRNA vaccines in antigen presenting cells remains a key barrier to eliciting potent antitumor immune responses. Herein, we develop dendritic cells (DCs) targeting LNPs by taking advantage of mannose receptor-mediated endocytosis. Efficient delivery of mRNA to DCs is achieved in vitro and in vivo utilizing the sweet LNPs (STLNPs-Man). Intramuscular injection of mRNA vaccine (STLNPs-Man@mRNAOVA ) results in a four-fold higher uptake by DCs in comparison with commercially used LNPs. Benefiting from its DCs targeting ability, STLNPs-Man@mRNAOVA significantly promotes the antitumor performances, showing a comparable therapeutic efficacy by using one-fifth of the injection dosage as the vaccine prepared from normal LNPs, thus remarkably avoiding the side effects brought by conventional mRNA vaccines. More intriguingly, STLNPs-Man@mRNAOVA exhibits the ability to downregulate the expression of cytotoxic T-lymphocyte-associated protein 4 on T cells due to the blockade of CD206/CD45 axis, showing brilliant potentials in promoting antitumor efficacy combined with immune checkpoint blockade therapy.
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Vacinas Anticâncer , Lipossomos , Nanopartículas , Neoplasias , Humanos , Apresentação de Antígeno , Vacinas de mRNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células Dendríticas/metabolismo , Neoplasias/terapia , Neoplasias/metabolismoRESUMO
Paraffin odor intensity is an important quality indicator when a paraffin inspection is performed. Currently, paraffin odor level assessment is mainly dependent on an artificial sensory evaluation. In this paper, we developed a paraffin odor analysis system to classify and grade four kinds of paraffin samples. The original feature set was optimized using Principal Component Analysis (PCA) and Partial Least Squares (PLS). Support Vector Machine (SVM), Random Forest (RF), and Extreme Learning Machine (ELM) were applied to three different feature data sets for classification and level assessment of paraffin. For classification, the model based on SVM, with an accuracy rate of 100%, was superior to that based on RF, with an accuracy rate of 98.33-100%, and ELM, with an accuracy rate of 98.01-100%. For level assessment, the R² related to the training set was above 0.97 and the R² related to the test set was above 0.87. Through comprehensive comparison, the generalization of the model based on ELM was superior to those based on SVM and RF. The scoring errors for the three models were 0.0016-0.3494, lower than the error of 0.5-1.0 measured by industry standard experts, meaning these methods have a higher prediction accuracy for scoring paraffin level.
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Wound infections are an escalating clinical challenge with continuous inflammatory response and the threat of drug-resistant bacteria. Herein, a series of self-healing conductive hydrogels were designed based on carboxymethyl chitosan/oxidized sodium alginate/polymerized gallic acid/Fe3+ (CMC/OSA/pGA/Fe3+, COGFe) for promoting infected wound healing. The Schiff base and catechol-Fe3+ chelation in the dynamical dual network structure of the hydrogels endowed dressings with good toughness, conductivity, adhesion, and self-healing properties, thus flexibly adapting to the deformation of skin wounds. In terms of ultraviolet (UV) resistance and scavenging of reactive oxygen species (ROS), the hydrogels significantly reduced oxidative stress at the wound site. Additionally, the hydrogels with photothermal therapy (PTT) achieved a 95% bactericidal rate in 5 min of near-infrared (NIR) light radiation by disrupting the bacterial cell membrane structure through elevated temperature. Meanwhile, the inherent antimicrobial properties of GA could reduce healthy tissue damage caused by excessive heat. The composite hydrogels could effectively promote the proliferation and migration of fibroblasts and possess good biocompatibility and hemostatic effect. In full-thickness infected wound repair experiments in rats, the COGFe5 hydrogel combined with NIR effectively killed bacteria, modulated macrophage polarization (M1 to M2 phenotype) to improve the immune microenvironment of the wound, and shortened the repair time by accelerating the expression of collagen deposition (TGF-ß) and vascular factors (CD31). This combined therapy might provide a prospective strategy for infectious wound treatment.
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Antibacterianos , Quitosana , Hidrogéis , Cicatrização , Hidrogéis/química , Hidrogéis/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Ratos , Quitosana/química , Quitosana/farmacologia , Quitosana/análogos & derivados , Antibacterianos/farmacologia , Antibacterianos/química , Camundongos , Terapia Fototérmica , Staphylococcus aureus/efeitos dos fármacos , Alginatos/química , Alginatos/farmacologia , Ratos Sprague-Dawley , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/patologia , Inflamação/tratamento farmacológico , Inflamação/patologia , MasculinoRESUMO
Marine polysaccharides (MPs) are an eco-friendly and renewable resource with a distinctive set of biological functions and are regarded as biological materials that can be in contact with tissues and body fluids for an extended time and promote tissue or organ regeneration. Skin tissue is easily invaded by the external environment due to its softness and large surface area. However, the body's natural physiological healing process is often too slow or suffers from the incomplete restoration of skin structure and function. Functional wound dressings are crucial for skin tissue engineering. Herein, popular MPs from different sources are summarized systematically. In particular, the structure-effectiveness of MP-based wound dressings and the physiological remodeling process of different wounds are reviewed in detail. Finally, the prospect of MP-based smart wound dressings is stated in conjunction with the wound microenvironment and provides new opportunities for high-value biomedical applications of MPs.
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Pele , Cicatrização , Bandagens , Engenharia Tecidual , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêuticoRESUMO
Azo dye methyl orange (MO) and shell rotting cause great environmental pollution. Most of the common dye adsorbents are difficult to produce, not environmentally friendly and it is always difficult to utilize the shell resources effectively. In this study, shell-based economical and environmentally friendly magnetic hydroxyapatite microsphere adsorbents (Fe3O4 @SiO2/HAP) were developed for the removal of MO from simulated wastewater by sol-gel and hydrothermal synthesis methods. The effects of solution pH, initial concentration, adsorption time and system temperature on the adsorption effect were investigated, and the repeat recovery performance was explored. The equilibrium adsorption data follow the Freundlich isotherm and pseudo-second-order kinetic curves, and the analysis indicates that the adsorption process is spontaneously exothermic. The adsorption capacities of MO were up to 94.48% and 88.94%, under the acidic environment of pH = 4, respectively, and had good recycling performance. The results provide a high-value utilization pathway for waste shell resources and focus on the removal of azo dyes. This is expected to provide new development ideas for the environmental hazards caused by acid dye wastewater discharged into rivers and oceans, as well as the problems of soil pollution and resource waste caused by weathering and corrosion of shells.
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Águas Residuárias , Poluentes Químicos da Água , Adsorção , Durapatita , Microesferas , Dióxido de Silício , Compostos Azo , Cinética , Fenômenos Magnéticos , Poluentes Químicos da Água/análise , Concentração de Íons de HidrogênioRESUMO
The clinical treatment of infected skin injuries caused by exogenous bacteria faces great challenges. Conventional therapeutic approaches are difficult to achieve synergistic effects of infection control and induction of skin regeneration. In this study, a novel tannic acid-based physically cross-linked double network hydrogel (PDH gel) was prepared on demand by covalent cross-linking of tannic acid (TA) with polyvinyl alcohol (PVA) and chelating ligand of TA with Fe3+. The homogeneity of the hydrogel was achieved by the action of glycol dispersant. With the anti-inflammatory and antioxidant properties of Fe3+ and TA, this hydrogel exhibited excellent antibacterial properties by achieving 99.69% and 99.36% bacterial inhibition against E.coli and S. aureus, respectively. Moreover, the PDH gel exhibits good biocompatibility, stretchability (up to 200%) and skin-friendliness. After 14 days of PDH-1 gel implantation in a rat model infected by S. aureus, the wound healing rate was as high as 95.21%. PDH gel-1 showed more granulation tissue, more pronounced blood vessels, higher collagen fiber density and good collagen deposition, and its recovery effect was better than that of PSH gel and PDH gel-2 in vivo. Hence, this study provides a novel avenue for the design of future clinical infected wound healing dressings.
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Anti-Infecciosos , Hidrogéis , Animais , Ratos , Hidrogéis/farmacologia , Staphylococcus aureus , Cicatrização , Antibacterianos/farmacologia , Escherichia coliRESUMO
Marine shell resources have received great attention from researchers owing to their unique merits such as high hardness, good toughness, corrosion resistance, high adsorption, and bioactivity. Restricted by the level of comprehensive utilization technology, the utilization rate of shells is extremely low, resulting in serious waste and pollution. The research shows that the unique brick-mud structure of shells makes them have diverse and good functional characteristics, which guides them to have great utilization potential in different fields. Hence, this review highlights the constitutive relationship between microstructure-function-application of shells (e.g., gastropods, cephalopods, and amniotes), and the comprehensive applications and development ideas in the fields of biomedicine, adsorption enrichment, pHotocatalysis, marine carbon sink, and environmental deicer. It is worth mentioning that marine shells are currently well developed in three areas: bone repair, health care and medicinal value, and drug carrier, which together promote the progress of biomedical field. In addition, an in-depth summary of the application of marine shells in the adsorption and purification of various impurities such as crude oil, heavy metal ions and dyes at low-cost and high efficiency is presented. Finally, by integrating thoughts and approaches from different applications, we are committed to providing new pathways for the excavation and future high-value of shell resources, clarifying the existing development stages and bottlenecks, promoting the development of related technology industries, and achieving the synergistic win-win situation of economic and environmental benefits.