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1.
Acta Biomater ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38897337

RESUMO

Antimicrobial phototherapy has gained recognition as a promising approach for addressing bacterial biofilms, however, its effectiveness is often impeded by the robust physical and chemical defenses of the biofilms. Traditional antibacterial nanoplatforms face challenges in breaching the extracellular polymeric substances barrier to efficiently deliver photosensitizers deep into biofilms. Moreover, the prevalent hypoxia within biofilms restricts the success of oxygen-reliant phototherapy. In this study, we engineered a soft mesoporous organosilica nanoplatform (SMONs) by incorporating polyethylene glycol (PEG), catalase (CAT), and indocyanine green (ICG), forming SMONs-PEG-CAT-ICG (SPCI). We compared the antimicrobial efficacy of SPCI with more rigid nanoplatforms. Our results demonstrated that unique flexible mechanical properties of SPCI enable it to navigate through biofilm barriers, markedly enhancing ICG penetration in methicillin-resistant Staphylococcus aureus (MRSA) biofilms. Notably, in a murine subcutaneous MRSA biofilm infection model, SPCI showed superior biofilm penetration and pharmacokinetic benefits over its rigid counterparts. The embedded catalase in SPCI effectively converts excess H2O2 present in infected tissues into O2, alleviating hypoxia and significantly boosting the antibacterial performance of phototherapy. Both in vitro and in vivo experiments confirmed that SPCI surpasses traditional rigid nanoplatforms in overcoming biofilm barriers, offering improved treatment outcomes for infections associated with bacterial biofilms. This study presents a viable strategy for managing bacterial biofilm-induced diseases by leveraging the unique attributes of a soft mesoporous organosilica-based nanoplatform. STATEMENT OF SIGNIFICANCE: This research introduces an innovative antimicrobial phototherapy soft nanoplatform that overcomes the inherent limitations posed by the protective barriers of bacterial biofilms. By soft nanoplatform with flexible mechanical properties, we enhance the penetration and delivery of photosensitizers into biofilms. The inclusion of catalase within this soft nanoplatform addresses the hypoxia in biofilms by converting hydrogen peroxide into oxygen in infected tissues, thereby amplifying the antibacterial effectiveness of phototherapy. Compared to traditional rigid nanoplatforms, this flexible nanoplatform not only promotes the delivery of therapeutic agents but also sets a new direction for treating bacterial biofilm infections, offering significant implications for future antimicrobial therapies.

2.
Nanoscale ; 16(24): 11669-11678, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38855849

RESUMO

Implant infections are severe complications in clinical treatment, which often accompany the formation of bacterial biofilms with high antibiotic resistance. Sonodynamic therapy (SDT) is an antibiotic-free method that can generate reactive oxygen species (ROS) to kill bacteria under ultrasound (US) treatment. However, the extracellular polymeric substances (EPS) barrier of bacterial biofilms and the hypoxic microenvironment significantly limit the antibiofilm activity of SDT. In this study, lipid-shelled perfluoropentane (PFP) nanodroplets loaded with gallium protoporphyrin IX (GaPPIX) and oxygen (O2) (LPGO NDs) were developed for the treatment of implant infections. Under US stimulation, LPGO NDs undergo the cavitation effect and disrupt the biofilm structure like bombs due to liquid-gas phase transition. Meanwhile, the LPGO NDs release O2 and GaPPIX upon US stimulation. The released O2 can alleviate the hypoxic microenvironment in the biofilm and enhance the ROS formation by GaPPIX for enhanced bacterial killing. In vivo experimental results demonstrate that the LPGO NDs can efficiently treat implant infections of methicillin-resistant Staphylococcus aureus (MRSA) in a mouse model by disrupting the biofilm structure, alleviating hypoxia, and enhancing bacterial killing by SDT. Therefore, this work provides a new multifunctional sonosensitizer to overcome the limitations of SDT for treating implant infections.


Assuntos
Biofilmes , Fluorocarbonos , Gálio , Staphylococcus aureus Resistente à Meticilina , Oxigênio , Protoporfirinas , Infecções Estafilocócicas , Terapia por Ultrassom , Animais , Fluorocarbonos/química , Fluorocarbonos/farmacologia , Camundongos , Gálio/química , Gálio/farmacologia , Protoporfirinas/química , Protoporfirinas/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Oxigênio/química , Infecções Estafilocócicas/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Nanopartículas/química , Antibacterianos/farmacologia , Antibacterianos/química , Camundongos Endogâmicos BALB C , Feminino , Pentanos
3.
ACS Nano ; 18(23): 15204-15217, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38803167

RESUMO

The Pseudomonas aeruginosa biofilm in recalcitrant chronic lung infections not only develops high antimicrobial tolerance but also induces an aberrant host inflammatory response. The metabolic condition plays a vital role in both the antimicrobial susceptibility of bacteria and the inflammatory response of immune cells, thereby offering a potential therapeutic target. Herein, we described a metabolic modulation strategy by using ultrasound-responsive liposomal nanoparticles containing a sonosensitizer and a hypoxia-activated prodrug against biofilm-associated chronic lung infections. Under ultrasound stimulation, the sonosensitizer generates antibacterial reactive oxygen species by oxygen consumption. Subsequently, the oxygen consumption-mediated hypoxia not only induces the anaerobic metabolism of bacteria for antibiotic activation but also triggers the glycolysis pathway of immune cells for inflammatory activation. Such metabolic modulation strategy demonstrated efficient therapeutic efficacy for P. aeruginosa biofilm-induced chronic lung infections in mice models and provides a promising way for combating biofilm-associated chronic infections.


Assuntos
Antibacterianos , Biofilmes , Infecções por Pseudomonas , Pseudomonas aeruginosa , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Pseudomonas aeruginosa/efeitos dos fármacos , Camundongos , Biofilmes/efeitos dos fármacos , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/imunologia , Nanopartículas/química , Lipossomos/química , Doença Crônica , Espécies Reativas de Oxigênio/metabolismo , Pró-Fármacos/farmacologia , Pró-Fármacos/química
4.
Small ; : e2400927, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38726949

RESUMO

Due to the presence of spatial barriers, persistent bacteria, and excessive inflammation in bacteria biofilm-infected wounds, current nanoplatforms cannot effectively address these issues simultaneously during the therapeutic process. Herein, a novel biomimetic photothermal nanoplatform integrating silver and polydopamine nanoparticles (Ag/PDAs) that can damage biofilms, kill bacterial persisters, and reduce inflammation for wound treatment is presented. These findings reveal that Ag/PDAs exhibit a broad-spectrum antimicrobial activity through direct damage to the bacterial membrane structure. Additionally, Ag/PDAs demonstrate a potent photothermal conversion efficiency. When combined with near-infrared (NIR) irradiation, Ag/PDAs effectively disrupt the spatial structure of biofilms and synergistically eradicate the resident bacteria. Furthermore, Ag/PDAs show remarkable anti-inflammatory properties in counteracting bacterium-induced macrophage polarization. The in vivo results confirm that the topical application of Ag/PDAs significantly suppress Staphylococcus aureus biofilm-infected wounds in murine models, concurrently facilitating wound healing. This research provides a promising avenue for the eradication of bacterial biofilms and the treatment of biofilm-infected wounds.

5.
Nano Lett ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38606881

RESUMO

Photocatalysis offers a direct, yet robust, approach to eradicate pathogenic bacteria. However, the practical implementation of photocatalytic disinfection faces a significant challenge due to low-efficiency photogenerated carrier separation and transfer. Here, we present an effective approach to improve photocatalytic disinfection performance by exploiting the pyro-phototronic effect through a synergistic combination of pyroelectric properties and photocatalytic processes. A set of comprehensive studies reveals that the temperature fluctuation-induced pyroelectric field promotes photoexcited carrier separation and transfer and thus facilitates the generation of reactive oxygen species and ultimately enhances photocatalytic disinfection performance. It is worth highlighting that the constructed film demonstrated an exceptional antibacterial efficiency exceeding 95% against pathogenic bacteria under temperature fluctuations and light irradiation. Moreover, the versatile modulation role of the pyro-phototronic effect in boosting photocatalytic disinfection was corroborated. This work paves the way for improving photocatalytic disinfection efficiency by harnessing the synergistic potential of various inherent material properties.

6.
Comput Biol Med ; 174: 108415, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38599070

RESUMO

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that requires objective and accurate identification methods for effective early intervention. Previous population-based methods via functional connectivity (FC) analysis ignore the differences between positive and negative FCs, which provide the potential information complementarity. And they also require additional information to construct a pre-defined graph. Meanwhile, two challenging demand attentions are the imbalance of performance caused by the class distribution and the inherent heterogeneity of multi-site data. In this paper, we propose a novel dynamic graph Transformer network based on dual-view connectivity for ASD Identification. It is based on the Autoencoders, which regard the input feature as individual feature and without any inductive bias. First, a dual-view feature extractor is designed to extract individual and complementary information from positive and negative connectivity. Then Graph Transformer network is innovated with a hot plugging K-Nearest Neighbor (KNN) algorithm module which constructs a dynamic population graph without any additional information. Additionally, we introduce the PolyLoss function and the Vrex method to address the class imbalance and improve the model's generalizability. The evaluation experiment on 1102 subjects from the ABIDE I dataset demonstrates our method can achieve superior performance over several state-of-the-art methods and satisfying generalizability for ASD identification.


Assuntos
Algoritmos , Transtorno do Espectro Autista , Transtorno do Espectro Autista/fisiopatologia , Transtorno do Espectro Autista/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Criança , Masculino , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Redes Neurais de Computação , Feminino
7.
Artigo em Inglês | MEDLINE | ID: mdl-38593051

RESUMO

In clinical settings, saliva has been established as a straightforward, noninvasive medium for diagnosing periodontitis. However, the precise diagnosis is often hampered by the absence of a specialized analyzer capable of detecting low concentrations of biomarkers typically found in saliva. In this study, we present a noninvasive, on-site screen-printed biomicrochip specifically engineered for the precise and sensitive quantification of lactate concentrations in saliva, a critical biomarker in the diagnosis of periodontitis. The microchip is constructed using a nanostructured ink formulation that includes MnFe@N-doped carbon nanotubes (MnFe@N-CNTs). These MnFe@N-CNTs exhibit a high degree of graphitization and low electrical resistance, significantly augmenting the electrocatalytic efficiency of the enzymatic reaction of lactate. This results in doubled sensitivity and a detection limit that surpasses those of the current advanced salivary assay methods. Remarkably, within just 30 s, the biomicrochip can quantitatively and precisely measure lactate concentrations in the saliva of 10 patients, which provides valuable insights into the severity of their periodontitis. This biosensor holds excellent potential for large-scale production and could broaden the scope of biomarker recognition, paving the way for the analysis of a wider range of oral diseases.

8.
Adv Healthc Mater ; 13(15): e2304355, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38387159

RESUMO

Amyloid beta-protein (AßAß) is a main hallmark of Alzheimer's disease (AD), and a low amount of Aß protein accumulation appears to be a potential marker for AD. Here, an electrochemical DNA biosensor based on polyamide/polyaniline carbon nanotubes (PA/PANI-CNTs) is developed with the aim of diagnosing AD early using a simple, low-cost, and accessible method to rapidly detect Aß42 in human blood. Electrospun PA nanofibers served as the skeleton for the successive in situ deposition of PANI and CNTs, which contribute both high conductivity and abundant binding sites for the Aß42 aptamers. After the aptamers are immobilized, this aptasensor exhibits precise and specific detection of Aß42 in human blood within only 4 min with an extremely fast response rate, lower detection limit, and excellent linear detection range. These findings make a significant contribution to advancing the development of serum-based detection techniques for Aß42, thereby paving the way for improved diagnostic capabilities in the field of AD.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Aptâmeros de Nucleotídeos , Biomarcadores , Técnicas Biossensoriais , Técnicas Eletroquímicas , Nanofibras , Nanotubos de Carbono , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/sangue , Humanos , Nanofibras/química , Peptídeos beta-Amiloides/sangue , Peptídeos beta-Amiloides/análise , Peptídeos beta-Amiloides/metabolismo , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Biomarcadores/sangue , Nanotubos de Carbono/química , Aptâmeros de Nucleotídeos/química , Compostos de Anilina/química , Limite de Detecção , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/sangue , Nylons/química
9.
J Prosthodont ; 33(3): 266-272, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36951153

RESUMO

PURPOSE: To investigate the distribution of marginal excess cement in vented and non-vented crowns and evaluate the effect of clinical cleaning procedures on the reduction of excess cement. MATERIALS AND METHODS: Forty models with implant analogs in the position of the right maxillary first molar were divided into four groups (n = 10/group, vented/non-vented crowns with or without cleaning procedures). The abutment finish lines were placed 1 mm below the artificial gingiva buccally, mesially, and distally and at the gingival level palatally. A standardized amount (20 mg) of resin cement was applied in a thin layer to the intaglio surface of zirconia vented and non-vented crowns. The excess cement was removed by a dental explorer in groups with cleaning procedures. The distribution (area and depth) of the marginal excess cement was measured at each quadrant (buccal, mesial, palatal, and distal) for all study samples. The data were analyzed using descriptive and analytical statistics (ɑ = 0.05). RESULTS: The area and depth values of the excess cement in each quadrant in the vented group were significantly smaller than that in the non-vented group, both with and without cleaning (p < 0.001). Cleaning procedures significantly reduced the area of excess cement in both vented and non-vented groups (all, p < 0.001 except for p < 0.05 at the buccal aspect of the vented group). The depth of excess cement in the vented group was significantly decreased with cleaning in the buccal quadrant compared with that without cleaning (p < 0.01). However, the depth of excess cement of the non-vented group was significantly increased with cleaning in all quadrants compared with that without cleaning (all, p < 0.001 except for p < 0.05 at the distal aspect). CONCLUSIONS: Crown venting significantly reduced the area and depth of the marginal excess cement in vitro. Cleaning procedure with a dental explorer significantly reduced the area of marginal excess cement in vitro; however, the excess cement can be pushed deeper in the non-vented group.


Assuntos
Cimentação , Implantes Dentários , Zircônio , Cimentação/métodos , Cimentos Dentários , Cimentos de Ionômeros de Vidro , Coroas , Prótese Dentária Fixada por Implante , Dente Suporte
10.
J Colloid Interface Sci ; 657: 611-618, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38071810

RESUMO

Nanozymes hold great prospects for bacteria-infected wound management, yet the spatial control of their catalytic activity in infected area and normal tissues remains mired by the heterogeneity of tissue microenvironment. Here, we develop a novel two-dimensional ternary chalcogenide nanodots (Cu2MoS4, CMS NDs) with renal clearable ability and controlled catalytic activity for bacteria-infected wound treatment. The two-dimensional CMS NDs (∼4 nm) are prepared by a simple microwave-assisted chemical synthetic route. Our results show that CMS NDs not only have peroxidase-like activity in a pH-dependent manner (pH < 5.5). Based on the generation of hydroxyl radical (OH) by adding H2O2, CMS NDs show > 2 log bacterial inactivation for both Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Escherichia coli (E. coli) under the acidic condition. Moreover, CMS NDs show good biocompatibility and can be excreted by the kidney in mice. In vivo results display that CMS NDs show good therapeutic effect against bacteria infected wound in the presence of H2O2, but no damage for normal tissues. Taken together, this work provides a renal clearable two-dimensional nanozyme with spatially controlled catalytic activity for the treatment of wounds and bacterial infections on the skin surface.


Assuntos
Infecções Bacterianas , Staphylococcus aureus Resistente à Meticilina , Camundongos , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Escherichia coli , Peróxido de Hidrogênio/química
11.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1016555

RESUMO

Objective@#To investigate the osteogenic properties of a methacrylated gelatin (GelMA) / bone marrow mesenchymal stem cells (BMSCs) composite hydrogel applied to the skull defect area of rats and to provide an experimental basis for the development of bone regeneration biomaterials.@*Methods@#This study was approved by the Animal Ethics Committee of Nanjing University. A novel photocurable composite biohydrogel was developed by constructing photoinitiators [lthium phenyl (2,4,6-trimethylbenzoyl) phosphinate, LAP], GelMA, and BMSCs. The surface morphology and elemental composition of the gel were examined using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). The compressive strength of the gel was evaluated using an electronic universal testing machine. After in vitro culture for 1, 2, and 5 days, the proliferation of the BMSCs in the hydrogels was assessed using a CCK-8 assay, and their survival and morphology were examined through confocal microscopy. A 5 mm critical bone deficiency model was generated in a rat skull. The group receiving composite hydrogel treatment was referred to as the GelMA/BMSCs group, whereas the untreated group served as the control group. At the 4th and 8th weeks, micro-CT scans were taken to measure the bone defect area and new bone index, while at the 8th week, skull samples from the defect area were subjected to H&E staining, van Gieson staining, and Goldner staining to evaluate the quality of bone regeneration and new bone formation.@*Results@#SEM observed that the solidified GelMA showed a 3D spongy gel network with uniform morphology, the porosity of GelMA was 73.41% and the pore size of GelMA was (28.75 ± 7.13) μm. EDX results showed that C and O were evenly distributed in the network macroporous structure of hydrogel. The hydrogel compression strength was 152 kPa. On the 5th day of GelMA/BMSCs culture, the cellular morphology transitioned from oval to spindle shaped under microscopic observation, accompanied by a significant increase in cell proliferation (159.4%, as determined by the CCK-8 assay). At 4 weeks after surgery, a 3D reconstructed micro-CT image revealed a minimal reduction in bone defect size within the control group and abundant new bone formation in the GelMA/BMSCs group. At 8 weeks after surgery, no significant changes were observed in the control group's bone defect area, with only limited evidence of new bone growth; however, substantial healing of skull defects was evident in the GelMA/BMSCs group. Quantitative analysis at both the 4- and 8-week examinations indicated significant improvements in the new bone volume (BV), new bone volume/total bone volume (BV/TV), bone surface (BS), and bone surface/total bone volume (BS/TV) in the GelMA/BMSCs group compared to those in the control group (P<0.05). Histological staining showed continuous and dense formation of bone tissue within the defects in the GelMA/BMSCs group and only sporadic formation of new bone, primarily consisting of fibrous connective tissue, at the defect edge in the control group.@*Conclusion@#Photocuring hydrogel-based stem cell therapy exhibits favorable biosafety profiles and has potential for clinical application by inducing new bone formation and promoting maturation within rat skull defects.

12.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013085

RESUMO

Objective@#To evaluate the bone repair effect of 3D-printed magnesium (Mg)-loaded polycaprolactone (PCL) scaffolds in a rat skull defect model.@*Methods@#PCL scaffolds mixed with Mg microparticles were prepared by using 3D printing technology, as were pure PCL scaffolds. The surface morphologies of the two scaffolds were observed by scanning electron microscopy (SEM), and the surface elemental composition was analyzed via energy dispersive spectroscopy (EDS). The physical properties of the scaffolds were characterized through contact angle measurements and an electronic universal testing machine. This study has been reviewed and approved by the Ethics Committee. A critical size defect model was established in the skull of 15 Sprague-Dawley (SD) rats, which were divided into the PCL group, PCL-Mg group, and untreated group, with 5 rats in each group. Micro-CT scanning was performed to detect and analyze skull defect healing at 4 and 8 weeks after surgery, and samples from the skull defect area and major organs of the rats were obtained for histological staining at 8 weeks after surgery.@*Results@#The scaffolds had a pore size of (480 ± 25) μm, a fiber diameter of (300 ± 25) μm, and a porosity of approximately 66%. The PCL-Mg scaffolds contained 1.0 At% Mg, indicating successful incorporation of Mg microparticles. The contact angle of the PCL-Mg scaffolds was 68.97° ± 1.39°, indicating improved wettability compared to that of pure PCL scaffolds. Additionally, compared with that of pure PCL scaffolds, the compressive modulus of the PCL-Mg scaffolds was (57.37 ± 8.33) MPa, demonstrating enhanced strength. The PCL-Mg group exhibited the best bone formation behavior in the skull defect area compared with the control group and PCL group at 4 and 8 weeks after surgery. Moreover, quantitative parameters, such as bone volume (BV), bone volume/total volume (BV/TV), bone surface (BS), bone surface/total volume (BS/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N) and bone mineral density (BMD), of skull defects were better than those in the other groups, indicating the best bone regeneration effect. H&E, Goldner, and VG staining revealed more mineralized new bone formation in the PCL-Mg group than in the other groups, and H&E staining of the major organs revealed good biosafety of the material.@*Conclusion@#PCL-Mg scaffolds can promote the repair of bone defects and have clinical potential as a new scaffold material for the repair of maxillofacial bone defects.

13.
Adv Sci (Weinh) ; 11(10): e2307048, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38109089

RESUMO

Host immune systems serving as crucial defense lines are vital resisting mechanisms against biofilm-associated implant infections. Nevertheless, biofilms hinder the penetration of anti-bacterial species, inhibit phagocytosis of immune cells, and frustrate host inflammatory responses, ultimately resulting in the weakness of the host immune system for biofilm elimination. Herein, a cell-like construct is developed through encapsulation of erythrocyte membrane fragments on the surface of Fe3 O4 nanoparticle-fabricated microbubbles and then loaded with hydroxyurea (EMB-Hu). Under ultrasound (US) stimulation, EMB-Hu undergoes a stable oscillation manner to act in an "exocytosis" mechanism for disrupting biofilm, releasing agents, and enhancing penetration of catalytically generated anti-bacterial species within biofilms. Additionally, the US-stimulated "exocytosis" by EMB-Hu can activate pro-inflammatory macrophage polarization and enhance macrophage phagocytosis for clearance of disrupted biofilms. Collectively, this work has exhibited cell-like microbubbles with US-stimulated "exocytosis" mechanisms to overcome the biofilm barrier and signal macrophages for inflammatory activation, finally achieving favorable therapeutic effects against implant infections caused by methicillin-resistant Staphylococcus aureus (MRSA) biofilms.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Humanos , Microbolhas , Antibacterianos/farmacologia , Fagocitose , Macrófagos , Biofilmes , Complicações Pós-Operatórias
14.
Oncogenesis ; 12(1): 54, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37957153

RESUMO

The mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway is frequently reported to be hyperactivated in hepatocellular carcinoma (HCC) and contributes to HCC recurrence. However, the underlying regulatory mechanisms of mTORC1 signaling in HCC are not fully understood. In the present study, we found that the expression of kinesin family member 18B (KIF18B) was positively correlated with mTORC1 signaling in HCC, and the upregulation of KIF18B and p-mTOR was associated with a poor prognosis and HCC recurrence. Utilizing in vitro and in vivo assays, we showed that KIF18B promoted HCC cell proliferation and migration through activating mTORC1 signaling. Mechanistically, we identified Actin gamma 1 (γ-Actin) as a binding partner of KIF18B. KIF18B and γ-Actin synergistically modulated lysosome positioning, promoted mTORC1 translocation to lysosome membrane, and prohibited p70 S6K from entering lysosomes for degradation, which finally led to the enhancement of mTORC1 signaling transduction. Moreover, we found that KIF18B was a direct target of Forkhead box M1, which explains the potential mechanism of KIF18B overexpression in HCC. Our study highlights the potential of KIF18B as a therapeutic target for the treatment of HCC.

15.
World J Clin Cases ; 11(27): 6579-6586, 2023 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-37900244

RESUMO

BACKGROUND: Toripalimab and anlotinib have shown good response in esophageal cancer, with high objective response rate and progression free survival. Thus, they have been approved as second-line or above-line therapy for advanced or unresectable esophageal carcinoma. Combination of these two drugs may have synergistic effects, but evidence of which is lacking. CASE SUMMARY: Here, we report on a 73-year-old male, newly diagnosed with advanced esophageal squamous cell carcinoma (ESCC), who received a combination of toripalimab and anlotinib. Complete response was achieved after treatment for 3 mo and remission was maintained up to 14 mo. CONCLUSION: The combination therapy of toripalimab and anlotinib is a promising treatment for unresectable ESCC and related clinical trials are warranted.

16.
Bioinformatics ; 39(10)2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37851379

RESUMO

MOTIVATION: Gene regulatory networks (GRNs) are a way of describing the interaction between genes, which contribute to revealing the different biological mechanisms in the cell. Reconstructing GRNs based on gene expression data has been a central computational problem in systems biology. However, due to the high dimensionality and non-linearity of large-scale GRNs, accurately and efficiently inferring GRNs is still a challenging task. RESULTS: In this article, we propose a new approach, iLSGRN, to reconstruct large-scale GRNs from steady-state and time-series gene expression data based on non-linear ordinary differential equations. Firstly, the regulatory gene recognition algorithm calculates the Maximal Information Coefficient between genes and excludes redundant regulatory relationships to achieve dimensionality reduction. Then, the feature fusion algorithm constructs a model leveraging the feature importance derived from XGBoost (eXtreme Gradient Boosting) and RF (Random Forest) models, which can effectively train the non-linear ordinary differential equations model of GRNs and improve the accuracy and stability of the inference algorithm. The extensive experiments on different scale datasets show that our method makes sensible improvement compared with the state-of-the-art methods. Furthermore, we perform cross-validation experiments on the real gene datasets to validate the robustness and effectiveness of the proposed method. AVAILABILITY AND IMPLEMENTATION: The proposed method is written in the Python language, and is available at: https://github.com/lab319/iLSGRN.


Assuntos
Algoritmos , Redes Reguladoras de Genes , Biologia de Sistemas , Algoritmo Florestas Aleatórias , Fatores de Tempo , Biologia Computacional/métodos
17.
Int J Nanomedicine ; 18: 4601-4616, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37600119

RESUMO

Background: Inflammatory bowel disease (IBD) is closely related to higher intracellular oxidative stress. Therefore, developing a novel method to scavenge the harmful reactive oxygen species (ROS) and alleviate colon inflammation to treat IBD is a promising strategy. Methods: CeO2@PDA-PEG (CeO2@PP) were synthesized by modifying ceria (CeO2) nanorods with polydopamine (PDA) and polyethylene glycol (PEG). The ROS scavenging ability of CeO2@PP was detected by using flow cytometry and confocal laser scanning microscope (CLSM). The anti-inflammatory ability of CeO2@PP was determined in vitro by treating lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The biocompatibility of CeO2@PP was evaluated in vivo and in vitro. Moreover, the therapeutic effects of CeO2@PP in vivo were estimated in a dextran sulfate sodium salt (DSS)-induced colitis mouse model. Results: Physicochemical property results demonstrated that PDA and PEG modification endowed CeO2 nanorods with excellent dispersibility and colloidal stability. CeO2@PP maintained superior enzyme-like activity, including superoxide dismutase (SOD) and catalase (CAT), indicating antioxidant ability. Moreover, in vitro results showed that CeO2@PP with PDA promotes LPS-induced RAW 264.7 macrophages into M2-type polarization. In addition, in vitro and in vivo results showed that CeO2@PP have great biocompatibility and biosafety. Animal experiments have shown that CeO2@PP have excellent anti-inflammatory effects against DSS-induced colitis and effectively alleviated intestinal mucosal injury. Conclusion: The nanoplatform CeO2@PP possessed excellent antioxidant and anti-inflammatory properties for scavenging ROS and modulating macrophage polarization, which is beneficial for efficient colitis therapy.


Assuntos
Colite , Sequestradores de Radicais Livres , Indóis , Nanotubos , Polímeros , Espécies Reativas de Oxigênio , Indóis/química , Indóis/farmacologia , Indóis/uso terapêutico , Polímeros/química , Polímeros/farmacologia , Polímeros/uso terapêutico , Colite/tratamento farmacológico , Colite/patologia , Inflamação/tratamento farmacológico , Inflamação/patologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Sequestradores de Radicais Livres/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Polaridade Celular , Cério , Animais , Camundongos , Células RAW 264.7 , Masculino , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
18.
Small ; 19(52): e2304127, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37649207

RESUMO

Antibacterial theranostic nanoplatforms, which integrate diagnostic and therapeutic properties, exhibit gigantic application prospects in precision medicine. However, traditional theranostic nanoplatforms usually present an always-on signal output, which leads to poor specificity or selectivity in the treatment of bacterial infections. To address this challenge, stimuli-actuated turn-on nanoplatforms are developed for simultaneous activation of diagnostic signals (e.g., fluorescent, photoacoustic, magnetic signals) and initiation of antibacterial treatment. Specifically, by combining the infection microenvironment-responsive activation of visual signals and antibacterial activity, these theranostic nanoplatforms exert both higher accurate diagnosis rates and more effective treatment effects. In this review, the imaging and treatment strategies that are commonly used in the clinic are first briefly introduced. Next, the recent progress of stimuli-actuated turn-on theranostic nanoplatforms for treating bacterial infectious diseases is summarized in detail. Finally, current bottlenecks and future opportunities of antibacterial theranostic nanoplatforms are also outlined and discussed.


Assuntos
Neoplasias , Medicina de Precisão , Humanos , Nanomedicina Teranóstica/métodos , Diagnóstico por Imagem , Neoplasias/tratamento farmacológico , Microambiente Tumoral
19.
ACS Appl Mater Interfaces ; 15(34): 40369-40377, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37594304

RESUMO

The chlorine evolution reaction (CER) is a key reaction in electrochemical oxidation (EO) of water treatment. Conventional anodes based on platinum group metals can be prohibitively expensive, which hinders further application of EO systems. Crystalline cobalt antimonate (CoSbxOy) was recently identified as a promising alternative to conventional anodes due to its high catalytic activity and stability in acidic media. However, its catalytic sites and reaction mechanism have not yet been elucidated. This study sheds light on the catalytically active sites in crystalline CoSbxOy anodes by using scanning electrochemical microscopy to compare the CER catalytic activities of a series of anode samples with different bulk Sb/Co ratios (from 1.43 to 2.80). The results showed that Sb sites served as more active catalytic sites than the Co sites. The varied Sb/Co ratios were also linked with slightly different electronic states of each element, leading to different CER selectivities in 30 mM chloride solutions under 10 mA cm-2 current density. The high activity of Sb sites toward the CER highlighted the significance of the electronic polarization that changed the oxidation states of Co and Sb.

20.
J Nanobiotechnology ; 21(1): 236, 2023 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-37482608

RESUMO

Therapeutic tumor vaccines have attracted considerable attention in the past decade; they can induce tumor regression, eradicate minimal residual disease, establish lasting immune memory and avoid non-specific and adverse side effects. However, the challenge in the field of therapeutic tumor vaccines is ensuring the delivery of immune components to the lymph nodes (LNs) to activate immune cells. The clinical response rate of traditional therapeutic tumor vaccines falls short of expectations due to inadequate lymph node delivery. With the rapid development of nanotechnology, a large number of nanoplatform-based LN-targeting nanovaccines have been exploited for optimizing tumor immunotherapies. In addition, some nanovaccines possess non-invasive visualization performance, which is benefit for understanding the kinetics of nanovaccine exposure in LNs. Herein, we present the parameters of nanoplatforms, such as size, surface modification, shape, and deformability, which affect the LN-targeting functions of nanovaccines. The recent advances in nanoplatforms with different components promoting LN-targeting are also summarized. Furthermore, emerging LNs-targeting nanoplatform-mediated imaging strategies to both improve targeting performance and enhance the quality of LN imaging are discussed. Finally, we summarize the prospects and challenges of nanoplatform-based LN-targeting and /or imaging strategies, which optimize the clinical efficacy of nanovaccines in tumor immunotherapies.


Assuntos
Vacinas Anticâncer , Neoplasias , Humanos , Linfonodos , Neoplasias/terapia , Imunoterapia , Nanotecnologia
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