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1.
J Hazard Mater ; 443(Pt B): 130289, 2023 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-36345059

RESUMO

Ultrasensitive real-time detection of trace Pb2+ in continuous flow is vital to effectively and timely eliminate the potential hazards to ecosystem health and sustainability. This work reports on a micro-structured smart hydrogel grating with ultra-sensitivity, high selectivity, good transparency and mechanical property for real-time detection of Pb2+ in continuous flow. The hydrogel grating possesses uniform surface relief microstructures with periodic nano-height ridges made of poly(acrylamide-co-benzo-18-crown-6-acrylamide) networks that crosslinked by tetra-arm star poly(ethylene glycol)acrylamide. The hydrogel grating with good optical transparency and mechanical property can change its height via selective host-guest complexation with Pb2+ to output a changed diffraction efficiency. Meanwhile, the periodic nano-ridges with large specific area benefit the contact with Pb2+ for fast Pb2+-induced height change. Thus, with such rationally designed molecular structures and surface relief microstructures, the hydrogel grating integrated in a glass-based mini-chip allows real-time detection of Pb2+ in continuous flow with ultra-sensitivity and high selectivity. The hydrogel grating detector can achieve ultralow detection limit (10-9 M Pb2+), fast response (2 min), and selective detection of Pb2+ from dozens of interfering ions even with high concentrations. This high-performance hydrogel grating detector is general and can be extended to detect many analytes due to the wide choice of responsive hydrogels, thus opening new areas for creating advanced smart detectors in analytical science.


Assuntos
Hidrogéis , Chumbo , Hidrogéis/química , Ecossistema , Íons/química , Acrilamida
2.
J Hazard Mater ; 442: 130072, 2023 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-36303342

RESUMO

Antimony (Sb) pollution in the water environment caused by the large-scale mining of Sb ore and the wide use of Sb-containing products seriously endangers human health and poses a great threat to the ecological environment. Coagulation is one of the most cost-effective technologies for Sb pollution control in water/wastewater treatment and has been widely used. However, a comprehensive understanding of Sb pollution control by coagulation, from fundamental research to practical applications, is lacking. In this work, based on the current status of Sb pollution in the water environment, a critical review of the Sb removal performance and mechanism by coagulation and related combined processes was carried out. The influencing factors of Sb removal performance by coagulation are introduced in detail. The internal mechanisms and improvement strategies of Sb removal by oxidation/reduction-coagulation and coagulation-membrane filtration technologies are emphasized. Moreover, given the development of Sb-removing coagulants and the resource utilization of Sb-containing sludge, future perspectives of coagulation for Sb removal are discussed. As the first review in this field, this work will illuminate avenues of basic research and practical applications for Sb and Sb-like pollution control in water/wastewater treatment.


Assuntos
Poluentes Químicos da Água , Purificação da Água , Humanos , Águas Residuárias , Antimônio , Água , Poluentes Químicos da Água/análise
3.
Lab Chip ; 22(24): 4962-4973, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36420612

RESUMO

Controllable mass production of monodisperse droplets plays a key role in numerous fields ranging from scientific research to industrial application. Microfluidic ladder networks show great potential in mass production of monodisperse droplets, but their design with uniform microflow distribution remains challenging due to the lack of a rational design strategy. Here an effective design strategy based on backstepping microflow analysis (BMA) is proposed for the rational development of microfluidic ladder networks for mass production of controllable monodisperse microdroplets. The performance of our BMA rule for rational microfluidic ladder network design is demonstrated by using an existing analogism-derived rule that is widely used for the design of microfluidic ladder networks as the control group. The microfluidic ladder network designed by the BMA rule shows a more uniform flow distribution in each branch microchannel than that designed by the existing rule, as confirmed by single-phase flow simulation. Meanwhile, the microfluidic ladder network designed by the BMA rule allows mass production of droplets with higher size monodispersity in a wider window of flow rates and mass production of polymeric microspheres from such highly monodisperse droplet templates. The proposed BMA rule provides new insights into the microflow distribution behaviors in microfluidic ladder networks based on backstepping microflow analysis and provides a rational guideline for the efficient development of microfluidic ladder networks with uniform flow distribution for mass production of highly monodisperse droplets. Moreover, the BMA method provides a general analysis strategy for microfluidic networks with parallel multiple microchannels for rational scale-up.

4.
Eur J Radiol ; 158: 110614, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36423365

RESUMO

PURPOSE: To evaluate an optimized 3D-real IR sequence with a longer TR (16,000 ms) based on the modulated flip angle technique in refocused imaging with extended echo train (MATRIX) for the endolymphatic hydrops (EH) after intravenous (IV) single-dose gadolinium (Gd) administration, and compare it with a heavily T2-weighted 3D-FLAIR sequence with a constant flip angle. METHOD: The 3D-FLAIR and 3D-real IR sequences were performed in forty patients with definite Meniere's disease (MD) four hours after IV Gd administration. Image qualities of the two sequences were rated and compared. Contrast-to-noise ratios (CNRs) and signal-to-noise ratios (SNRs) of the two sequences were measured for quantitative comparison. EH was graded on the images of the two sequences by two radiologists. RESULTS: Scores and CNRs of the 3D-real IR were significantly higher than those of the 3D-FLAIR (P < 0.05). SNRs of the two sequences were comparable between the two groups. 3D-real IR had a higher inter- and intra-observer reliability for the grading of cochlear and vestibular EH than 3D-FLAIR. Using 3D-real IR sequence, the detection rate of EH of the whole labyrinth was higher than using 3D-FLAIR (86.6 % vs 73.3 %, p = 0.031). In the patients with unilateral MD, SNRs in the affected sides were significantly higher than the unaffected sides (P < 0.05). CONCLUSIONS: The optimized 3D-real IR with a longer TR is a robust sequence with an improved depiction of EH after IV administration of single-dose Gd. Compared with 3D-FLAIR, it may allow a more precise evaluation and grading of EH.

5.
Adv Mater ; : e2204994, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36349821

RESUMO

Age-related macular degeneration (AMD) is a major cause of visual impairment and severe vision loss worldwide, while the currently available treatments are often unsatisfactory. Previous studies have demonstrated both inflammation and oxidative stress-induced damage to the retinal pigment epithelium (RPE) are involved in the pathogenesis of aberrant development of blood vessels in wet AMD (wet-AMD). Although anti-vascular endothelial growth factor (VEGF) therapy (e.g., Ranibizumab) can impair the growth of new blood vessels, side effects were still found with repeated monthly intravitreal injections. Here, an injectable antibody-loaded supramolecular nanofiber hydrogel is fabricated by simply mixing betamethasone phosphate (BetP), a clinic anti-inflammatory drug, anti-VEGF, the gold-standard anti-VEGF drug for AMD treatment, with CaCl2 . Upon intravitreal injection, such BetP-based hydrogel (BetP-Gel) while enabling long-term sustained release of anti-VEGF to inhibit vascular proliferation in the retina and attenuate choroidal neovascularization (CNV), could also scavenge reactive oxygen species (ROS) to reduce local inflammation. Remarkably, such BetP-Gel could dramatically prolong the effective treatment time of conventional anti-VEGF therapy. Notably, our anti-VEGF-loaded supramolecular hydrogel based on all clinically approved agents may be readily translated into clinical use for AMD treatment, with the potential to replace the current anti-VEGF therapy. This article is protected by copyright. All rights reserved.

6.
Front Oncol ; 12: 1014465, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36425554

RESUMO

Background: Intralesional injection of lauromacrogol has proven to be an efficient treatment method for infantile hemangioma. This study aims to explore a novel injection therapy and evaluate its efficacy and complications. Methods: The medical records of 368 children with infantile hemangioma who received a lauromacrogol injection from January 2021 to April 2022 were retrospectively analyzed. All patients were reviewed every 4 weeks, and their condition was assessed according to symptoms and medical records. The patient's age, lesion type, location, size and thickness, lesion photographs, ultrasound, and complications were recorded. Results: Among the 368 infants who accept sclerotherapy with lauromacrogol, 226(61.4%)achieved excellent regression. In total, 108(29.4%)cases achieved good regression. 24(6.5%)achieved complete moderate regression. 10(2.7%)achieved poor regression. The reported incidence of adverse events was 4.9% and severe complications were not observed. Before and after three courses of treatment, the median vascular endothelial growth factor levels were 104.12 pg/ml and 28.982 pg/ml. There was a significant difference between the two groups (P=0.0043). Conclusions: The results showed that this novel injection therapy a safe and effective treatment method. The therapy accelerated the regression of infantile hemangiomas without serious complications.

7.
Biomaterials ; 291: 121904, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36403323

RESUMO

Oxidative stress and mitochondrial damage are the main mechanisms of ischemia-reperfusion injury in ischemic stroke. Herein, cerium oxide nanoparticles with powerful free radical scavenging ability were used as carriers to load dl-3-n-butylphthalide (NBP-CeO2 NPs) for the combined treatment of ischemic stroke. NBP-CeO2 NPs could eliminate reactive oxygen species (ROS) in mouse brain microvascular endothelial cells and hippocampal neurons after oxygen-glucose deprivation/reoxygenation (OGD/R), and also save mitochondrial membrane potential, morphology, and function, thus alleviating the in vitro blood brain barrier (BBB) disruption and neuronal apoptosis. In the middle cerebral artery embolization/recanalization (MCAO/R) mouse model, the NBP-CeO2 NPs also possessed superior ROS scavenging ability, protected mitochondria, and preserved BBB integrity, thereby reducing cerebral infarction and cerebral edema and inhibiting neuroinflammation and neuronal apoptosis. The long-term neurobehavioral tests indicated that the NBP-CeO2 NPs significantly improved sensorimotor function and spatial learning ability by promoting angiogenesis after ischemic stroke. Therefore, the NBP-CeO2 NPs provided a novel therapeutic approach for ischemic stroke by combining antioxidant and neurovascular repair abilities, highlighting its wide application in ischemia-reperfusion injury.


Assuntos
AVC Isquêmico , Nanopartículas , Traumatismo por Reperfusão , Animais , Camundongos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Espécies Reativas de Oxigênio , Células Endoteliais , Traumatismo por Reperfusão/tratamento farmacológico
8.
Biomaterials ; 291: 121880, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36334355

RESUMO

Considering the huge cost and long test periods required for new drug development, repurposing drugs that have already been applied in the clinic as new cancer treatment candidates represents an attractive alternative. Disulfiram (DSF) was originally used to treat alcoholism and has proven to have anticancer effects with the coadministration of copper ions (Cu2+). However, the limited water-solubility of DSF and systemic toxicity induced by exogenous Cu2+ hinder its practical application. Herein, we constructed pH-responsive lipid-coated calcium phosphate nanoparticles (LCP NPs) co-loaded with Cu2+ and DSF. After intravenous injection, those nanoparticles with long blood half-life preferentially accumulate in tumors, followed by the degradation of nanoparticles in response to the acidic tumor microenvironment, subsequently releasing Cu2+ and DSF to generate cytotoxic metabolite DTC-Copper complex, bis(diethyldithiocarbamate)-copper (CuET) for tumor treatment. In addition to direct cytotoxicity, the active metabolite CuET could effectively induce immunogenic cell death (ICD) of cancer cells to regulate the immunosuppressive tumor microenvironment, contributing to enhanced immune checkpoint blockade (ICB) therapy in triggering systemic immune responses. This work thus demonstrates the great promises of repurposing the old drug DSF as a new ICD inducer with nano-formulation, to achieve improved synergetic tumor-responsive therapy with low side effects.


Assuntos
Antineoplásicos , Nanopartículas , Neoplasias , Dissulfiram/uso terapêutico , Dissulfiram/farmacologia , Cobre/farmacologia , Antineoplásicos/farmacologia , Fosfatos de Cálcio , Imunoterapia , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico
9.
Nat Commun ; 13(1): 6632, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36333329

RESUMO

In this paper, we report a unique type of core-shell crystalline material that combines an inorganic zeolitic cage structure with a macrocyclic host arrangement and that can remove trace levels of iodine from water effectively. These unique assemblies are made up of an inorganic Archimedean truncatedhexahedron (tcu) polyhedron in the kernel which possesses six calixarene-like shell cavities. The cages have good adaptability to guests and can be assembled into a series of supramolecular structures in the crystalline state with different lattice pore shapes. Due to the unique core-shell porous structures, the compounds are not only stable in organic solvents but also in water. The characteristics of the cages enable rapid iodine capture from low concentration aqueous I2/KI solutions (down to 4 ppm concentration). We have studied the detailed process and mechanism of iodine capture and aggregation at the molecular level. The facile synthesis, considerable adsorption capacity, recyclability, and ß- and γ-radiation resistance of the cages should make these materials suitable for the extraction of iodine from aqueous effluent streams (most obviously, radioactive iodide produced by atomic power generation).

10.
Small ; 18(48): e2204350, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36269872

RESUMO

Extracellular outer-membrane vesicles (OMVs) are attractive for use as drug nanocarriers, because of their high biocompatibility and ability to enter cells. However, widespread use is hampered by low yields. Here, a high-yield method for magnetic harvesting of OMVs from Escherichia coli is described. To this end, E. coli are grown in the presence of magnetic iron-oxide nanoparticles (MNPs). Uptake of MNPs by E. coli is low and does not increase secretion of OMVs. Uptake of MNPs can be enhanced through PEGylation of MNPs. E. coli growth in the presence of PEGylated MNPs increases bacterial MNP-uptake and OMV-secretion, accompanied by upregulation of genes involved in OMV-secretion. OMVs containing MNPs can be magnetically harvested at 60-fold higher yields than achieved by ultracentrifugation. Functionally, magnetically-harvested OMVs and OMVs harvested by ultracentrifugation are both taken-up in similar numbers by bacteria. Uniquely, in an applied magnetic field, magnetically-harvested OMVs with MNPs accumulate over the entire depth of an infectious biofilm. OMVs harvested by ultracentrifugation without MNPs only accumulate near the biofilm surface. In conclusion, PEGylation of MNPs is essential for their uptake in E. coli and yields magnetic OMVs allowing high-yield magnetic-harvesting. Moreover, magnetic OMVs can be magnetically targeted to a cargo delivery site in the human body.


Assuntos
Escherichia coli , Vesículas Extracelulares , Humanos , Biofilmes , Fenômenos Magnéticos
11.
Elife ; 112022 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-36226916

RESUMO

A fundamental question in protein science is where allosteric hotspots - residues critical for allosteric signaling - are located, and what properties differentiate them. We carried out deep mutational scanning (DMS) of four homologous bacterial allosteric transcription factors (aTFs) to identify hotspots and built a machine learning model with this data to glean the structural and molecular properties of allosteric hotspots. We found hotspots to be distributed protein-wide rather than being restricted to 'pathways' linking allosteric and active sites as is commonly assumed. Despite structural homology, the location of hotspots was not superimposable across the aTFs. However, common signatures emerged when comparing hotspots coincident with long-range interactions, suggesting that the allosteric mechanism is conserved among the homologs despite differences in molecular details. Machine learning with our large DMS datasets revealed global structural and dynamic properties to be a strong predictor of whether a residue is a hotspot than local and physicochemical properties. Furthermore, a model trained on one protein can predict hotspots in a homolog. In summary, the overall allosteric mechanism is embedded in the structural fold of the aTF family, but the finer, molecular details are sequence-specific.


Assuntos
Aprendizado de Máquina , Proteínas , Regulação Alostérica , Mutação , Proteínas/química , Transdução de Sinais , Simulação de Dinâmica Molecular
12.
Artigo em Inglês | MEDLINE | ID: mdl-36212944

RESUMO

Sick sinus syndrome (SSS) is closely associated with cardiac syncope and sudden death, wherein sinoatrial node (SAN) fibrosis is one of the main pathological changes that occur. Shenxian-Shengmai oral liquid (SXSM) has been clinically proven to significantly improve the heart rate of SSS patients. In this study, we aimed to explore the mechanism of SXSM in reducing the SAN fibrosis by combining in vitro and in vivo experiments. Accordingly, the SSS model was constructed by slowly pumping angiotensin II (AngII) with a micro-osmotic pump. The degree of fibrosis was evaluated by Masson's trichrome staining and immunofluorescence staining of the fibrosis marker protein. In addition, NIH-3T3 mouse fibroblasts were used to simulate SAN fibroblasts to further explore the mechanism, with AngII used as the cellular fibrosis inducer. Monodansylcadaverine (MDC) staining and transmission electron microscopy were employed to assay the autophagy content, whereas immunofluorescence staining and Western blotting were employed to elucidate the related protein expression. Finally, fibroblasts were given the AKT phosphorylation agonist SC79 to reversely verify the effects of SXSM. The results showed that SXSM could significantly increase the heart rate of SSS mice by reducing the deposition of extracellular matrix (ECM) in SAN induced by AngII. According to in vivo experiments, when compared with the model group, SSS mice treated with SXSM developed less fibrosis in the SAN area. In vitro experiments revealed that AngII could restrain autophagy by activating the phosphorylation of the AKT/mTOR pathway, thereby increasing the deposition of ECM. Moreover, SXSM pretreatment prevented this upregulation. After the intervention of SC79, the protective effect of SXSM was weakened. In conclusion, SXSM activated autophagy through the AKT/mTOR pathway, which in turn reduced the deposition of the ECM in SAN induced by AngII, attenuated the fibrosis of SAN, and improved the decreased heart rate in the SSS mice.

13.
Emerg Med Int ; 2022: 5371493, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36193543

RESUMO

Robotic surgery can provide less surgical trauma than conventional surgery, but differences between robotic and thoracoscopic surgery for atrial septal defect (ASD) repair are not well documented. To explore whether ASD can be repaired by thoracoscopic surgery or robotic surgery, which procedure is less invasive, and the difference in outcomes between these two procedures, this article studies 160 patients undergoing ASD repair at our institution. Sixty-five patients underwent total thoracoscopic surgery and 95 patients underwent total endoscopic robotic surgery. Propensity score matching yielded 64 well-matched patient pairs. Surgical data and early postoperative outcomes between the two matched groups were analyzed and compared. The results show that thoracoscopic and robotic surgery to repair ASD are both safe and reliable, and the early curative effect is good. However, regardless of similar complication rates, robotic surgery has a shorter time, less postoperative drainage, and faster recovery than thoracoscopic surgery.

14.
Oxid Med Cell Longev ; 2022: 8488269, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36199421

RESUMO

Population aging has led to increased sick sinus syndrome (SSS) incidence; however, no effective and safe medical therapy has been reported thus far. Yixin-Fumai granules (YXFMs), a Chinese medicine granule designed for bradyarrhythmia treatment, can effectively increase SSS patients' heart rate. Senescence-induced sinoatrial node (SAN) degeneration is an important part of SSS pathogenesis, and older people often show high levels of oxidative stress; reactive oxygen species (ROS) accumulation in the SAN causes abnormal SAN pacing or conduction functions. The current study observed the protective effects of YXFMs on senescent SAN and explored the relationship between the NRF-2/HO-1 pathway, SHOX2, and T-type calcium channels. We selected naturally senescent C57BL/6 mice with bradycardia to simulate SSS; electrocardiography, Masson's trichrome staining, and DHE staining were used to assess SAN function and tissue damage. Immunofluorescence staining and Western blotting were used to assay related proteins. In vitro, we treated human-induced pluripotent stem cell-derived atrial myocytes (hiPSC-AMs) and mouse atrial myocyte-derived cell line HL-1 with D-galactose to simulate senescent SAN-pacemaker cells. CardioExcyte96 was used to evaluate the pulsatile function of the hiPSC-AMs, and the mechanism was verified by DCFH-DA, immunofluorescence staining, RT-qPCR, and Western blotting. The results demonstrated that YXFMs effectively inhibited senescence-induced SAN hypofunction, and this effect possibly originated from scavenging of ROS and promotion of NRF-2, SHOX2, and T-type calcium channel expression. In vitro experiment results indicated that ML385, si-SHOX2, LDN193189, and Mibefradil reversed YXFMs' effects. Moreover, we, for the first time, found that ROS accumulation may hinder SHOX2 expression; YXFMs can activate SHOX2 through the NRF-2/HO-1 pathway-mediated ROS scavenging and then regulate CACNA1G through the SHOX2/BMP4/GATA4/NKX2-5 axis, improve T-type calcium channel function, and ameliorate the SAN dysfunction. Finally, through network pharmacology and molecular docking, we screened for the most stable YXFMs compound that docks to NRF-2, laying the foundation for future studies.


Assuntos
Canais de Cálcio Tipo T , Heme Oxigenase-1/metabolismo , Proteínas de Homeodomínio , Fator 2 Relacionado a NF-E2/metabolismo , Aceleração , Idoso , Animais , Galactose , Frequência Cardíaca , Proteínas de Homeodomínio/metabolismo , Humanos , Medicina Tradicional Chinesa , Mibefradil , Camundongos , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição/metabolismo
15.
Front Pediatr ; 10: 1011511, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36210935

RESUMO

[This corrects the article DOI: 10.3389/fped.2022.925318.].

16.
ACS Nano ; 16(11): 19328-19334, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36282211

RESUMO

Cytotoxic T lymphocytes (CTLs) are important immune cells, and their activation is a key step for cancer immunotherapy. Precise evaluation of CTL activity in vivo provides a powerful tool for monitoring cancer-immunotherapeutic outcomes, yet it faces tremendous challenges. Herein, by rationally designing a near-infrared (NIR) fluorescence probe Cys(StBu)-Ile-Glu-Phe-Asp-Lys(Cy5.5)-CBT (Cy5.5-CBT) and employing a reduction-instructed CBT-Cys click condensation reaction, we developed the fluorescence "dual quenched" nanoparticles Cy5.5-CBT-NPs for imaging of granzyme B (GraB), a biomarker tightly associated with the tumoricidal activity of CTLs. Upon GraB cleavage, Cy5.5-CBT-NPs disassembled, subtly turning the fluorescence signal "on". With this fluorescence "turn-on" property, Cy5.5-CBT-NPs enabled sensitive and real-time monitoring of GraB-mediated CTL responses against cancer cells in vitro. Animal experiments demonstrated that, at 16 h post injection, the fluorescence imaging signal of Cy5.5-CBT-NPs showed a 3.1-fold increase on the tumor sites of mice treated by an immune-activating drug S-(2-boronoethyl)-L-cysteine hydrochloride. We envision that Cy5.5-CBT-NPs may provide a powerful tool for noninvasive and sensitive evaluation of immunotherapeutic efficacy of cancer in the near future.


Assuntos
Nanopartículas , Neoplasias , Animais , Camundongos , Granzimas , Linfócitos T Citotóxicos , Carbocianinas , Neoplasias/diagnóstico por imagem , Neoplasias/terapia
17.
Adv Healthc Mater ; : e2201771, 2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36226993

RESUMO

Wound microenvironment with excess reactive oxygen species (ROS) can significantly inhibit wound healing. Encouraged by hydrogen molecules (H2 ) with effective ROS scavenging and calcium hydride (CaH2 ) with sufficient H2 supply, the authors for the first time employed CaH2 as a therapeutic H2 donor and starch as a diluent to construct CaH2 pulvis dressing for wound healing treatment. It has been found that CaH2 by generating H2 exhibited excellent ROS scavenging performance, favorable for preserving the oxidative-stress-induced cell death. After being applied onto the skin wound, the CaH2 pulvis dressing with the unique ROS-scavenging ability can accelerate skin wound healing in healthy/diabetic mice (small animal models) and Bama mini-pigs (large animal model). Such CaH2 dressing can release H2 to relieve the inflammation levels, decrease the secretion of pro-inflammatory cytokines, increase the infiltration of inflammation-suppressive immune cells, and promote the regeneration of new blood vessels and collagens, thereby accelerating wound healing. This work highlighted that the integration of anti-oxidation and anti-inflammation functions based on CaH2 dressing endowed it with a promising possibility for the treatment of inflammatory diseases.

18.
Colloids Surf B Biointerfaces ; 219: 112806, 2022 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-36088828

RESUMO

The poor bacteriostasis and osseointegration properties of bioinert polyetheretherketone (PEEK) hinder its clinical application. This work reports a simple and versatile strategy for fabricating dual-functional coating with programmed sequential drug release properties on porous PEEK surfaces. The dual-drug-loaded composite coating composed of drug-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles and drug-loaded polyvinyl alcohol (PVA) gel can be immobilized on the surface of sulfonated PEEK by a cyclic freeze-thaw method. Based on the swelling of PVA and the slow degradation of PLGA, the composite coating can realize rapid release of antibacterial drugs and sustained release of osteogenic drugs. The in vitro antibacterial evaluations show that the porous PEEK modified with drug-loaded composite gel coating exhibits an early effective fight against Staphylococcus aureus (S.aureus). The results of in vitro cell experiments show that the PEEK materials modified by the composite gel coating can well support the normal growth, adhesion and proliferation of cells. In addition, the PEEK material coated with the drug-loaded composite gel is found to have positive effects on the osteogenic differentiation of cells in detections of alkaline phosphatase (ALP) activity of cells and the amount of calcium deposition on the surface of the material. The results demonstrate that the proposed porous PEEK modified with dual-drug-loaded composite gel coating simultaneously exhibits excellent osseointegration and exerts early effective antibacterial activity. This dual-functional PEEK material has great application potential in clinical bone tissue repair.

19.
ACS Nano ; 16(9): 13884-13899, 2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36075132

RESUMO

Tumor hypoxia and acidity are well-known features in solid tumors that cause immunosuppression and therapeutic resistance. Herein, we rationally synthesized a multifunctional fluorinated calcium carbonate (fCaCO3) nanoregulator by coating CaCO3 nanoparticles with dopamine-grafted perfluorosebacic acid (DA2-PFSEA) and ferric ions by utilizing their coordination interaction. After PEGylation, the obtained fCaCO3-PEG showed high loading efficacy to perfluoro-15-crown-5-ether (PFCE), a type of perfluorocarbon with high oxygen solubility, thereby working as both oxygen nanoshuttles and proton sponges to reverse tumor hypoxia and acidity-induced resistance to radiotherapy. The as-prepared PFCE@fCaCO3-PEG could not only function as long-circulating oxygen nanoshuttles to attenuate tumor hypoxia but also neutralize the acidic tumor microenvironment by restricting the production of lactic acid and reacting with extracellular protons. As a result, treatment with PFCE@fCaCO3-PEG could improve the therapeutic outcome of radiotherapy toward two murine tumors with distinct immunogenicity. The PFCE@fCaCO3-PEG-assisted radiotherapy could also collectively inhibit the growth of unirradiated tumors and reject rechallenged tumors by synergistically eliciting protective antitumor immunity. Therefore, our work presents the preparation of fluorinated CaCO3 nanoregulators to reverse tumor immunosuppression and potentiate radiotherapy through chemically modulating tumor hypoxic and acidic microenvironments tightly associated with tumor glucose metabolism.


Assuntos
Fluorcarbonetos , Nanopartículas , Neoplasias , Animais , Carbonato de Cálcio , Linhagem Celular Tumoral , Dopamina , Glucose , Ácido Láctico , Camundongos , Neoplasias/metabolismo , Oxigênio , Prótons , Microambiente Tumoral
20.
Commun Biol ; 5(1): 1018, 2022 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-36167813

RESUMO

The formation of wound epithelium initiates regeneration of amputated tail in Gekko japonicus. Energy metabolism is indispensable for the growth of living creatures and typically influenced by temperature. In this study, we reveal that low temperature lowers energy metabolism level and inhibits the regeneration of amputated tails of Gekko japonicus. We further find that low temperature attenuates the activation of protein kinase B (Akt) and mammalian target of rapamycin (mTOR) in regenerated tissues upon injury signals, and the inhibition of Akt hinders proliferation of the wound epithelium. Additionally, wingless/integrated (Wnt) inhibition suppresses epithelium proliferation and formation by inhibiting Akt activation. Finally, low temperature elevates the activity of adenylate-activated kinase (AMPK) pathway and in turn attenuates wound epithelium formation. Meanwhile, either mTOR downregulation or AMPK upregulation is associated with worse wound epithelium formation. Summarily, low temperature restricts wound epithelium formation by influencing energy sensory pathways including Akt/mTOR and AMPK signaling, which is also modulated by injury induced Wnt signal. Our results provide a mechanism that incorporates the injury signals with metabolic pathway to facilitate regeneration.


Assuntos
Lagartos , Proteínas Proto-Oncogênicas c-akt , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Metabolismo Energético , Epitélio/metabolismo , Mamíferos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo
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