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1.
Small ; 20(11): e2305805, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37941516

RESUMEN

Microgrippers, a branch of micro/nanorobots, refer to motile miniaturized machines that are of a size in the range of several to hundreds of micrometers. Compared with tethered grippers or other microscopic diagnostic and surgical equipment, untethered microgrippers play an indispensable role in biomedical applications because of their characteristics such as miniaturized size, dexterous shape tranformation, and  controllable motion, which enables the microgrippers to enter hard-to-reach regions to execute specific medical tasks for disease diagnosis and treatment. To date, numerous medical microgrippers are developed, and their potential in cell manipulation, targeted drug delivery, biopsy, and minimally invasive surgery  are explored. To achieve controlled locomotion and efficient target-oriented actions, the materials, size, microarchitecture, and morphology of microgrippers shall be deliberately designed. In this review, the authors summarizes the latest progress in untethered micrometer-scale grippers. The working mechanisms of shape-morphing and actuation methods for effective movement are first introduced. Then, the design principle and state-of-the-art fabrication techniques of microgrippers are discussed. Finally, their applications in the precise medicine are highlighted, followed by offering future perspectives for the development of untethered medical microgrippers.


Asunto(s)
Sistemas de Liberación de Medicamentos , Medicina de Precisión , Biopsia/métodos , Movimiento (Física) , Predicción
2.
Aesthetic Plast Surg ; 47(5): 1843-1850, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37027031

RESUMEN

BACKGROUND: High crease correction is difficult to achieve in secondary blepharoplasty. Currently, patients tend to have more precise requirements for crease-lowering procedures, such as low in-fold or low out-fold creases. For the out-fold crease, the height of the central crease is similar with the height of the medial crease, whereas for the in-fold crease, the height of the medial crease is lower than the height of the central crease. OBJECTIVES: In this study, the authors developed a strategy to create low in-fold or out-fold creases to satisfy patients' individualized requirements. METHODS: The medical records of patients who received crease-lowering secondary blepharoplasty from January 2015 to January 2021 were reviewed. The results were grouped by preoperative condition (high in-fold/out-fold) and patients' expectations for postoperative outcome (low in-fold/out-fold). Preoperative and postoperative images were collected, and patient satisfaction, complications and revisions were evaluated. RESULTS: In total, 297 consecutive patients were included in this study with an average follow-up duration of 12.3 months. Eighteen patients had high in-fold creases, and 279 patients had high out-fold creases. Regarding patients with high out-folds, 233 patients wanted to have low out-folds, and 46 patients wanted to have low in-folds. Two hundred and sixty-six (89.6%) patients were satisfied with their results. Complications included complete crease loss (n = 3, 1.0%), partial crease loss (n = 5, 1.7%), multiple creases (n = 6, 2.0%), asymmetric creases (n = 7, 2.4%), and upper eyelid skin laxity (n = 10, 3.4%). CONCLUSIONS: This flexible, novel technique for customizing low out-fold or in-fold creases is reliable in high double-eyelid crease correction based on preoperative upper eyelid skin tightness, scar positions, and the patient's expected double-eyelid crease shape. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Asunto(s)
Blefaroplastia , Párpados , Humanos , Pueblo Asiatico , Blefaroplastia/métodos , Párpados/cirugía , Satisfacción del Paciente , Estudios Retrospectivos , Reoperación
3.
Aesthetic Plast Surg ; 46(5): 2287-2294, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35460042

RESUMEN

BACKGROUND: Double eyelid blepharoplasty is a popular procedure among Asian population. Double eyelid shape is important to achieving high satisfaction rate. Currently, there lacks large sample survey and detailed analysis on preferred double eyelid shape. This study aims to investigate the double eyelid shape preference using the "in-fold," "on-fold," and "out-fold" classification and analyze the preferred shape of different demographic groups. METHODS: A large sample survey was conducted with a questionnaire of nine questions in three sections: demographic characteristics, desired double eyelid shape, and assessment of the classification. The preference for each type of double eyelid shape was analyzed and compared among different groups. RESULTS: A total of 11153 (9698 female and 1455 male) respondents finished the questionnaire, including 382 plastic surgeons. In-fold double eyelid was the most popular choice overall. Out-fold was the least preferred, except for specific groups such as actors and heavy makeup wearers. No significant difference was observed between the preference of patients and plastic surgeons. The majority of respondents cared much about postoperative double eyelid shape and considered the classification useful. CONCLUSIONS: In-fold was the most preferred double eyelid shape, especially for patients who met one or more of the following criteria: male, older than 40, divorced, or housewives. However, heavy makeup wearers or actors/actresses tend to prefer out-fold double eyelids. The "in-fold," "on-fold," and "out-fold" classification was precise and beneficial to doctor-patient communication. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Asunto(s)
Blefaroplastia , Párpados , Humanos , Masculino , Femenino , Estudios Retrospectivos , Párpados/cirugía , Blefaroplastia/métodos , Pueblo Asiatico , Encuestas y Cuestionarios
4.
Small ; 15(36): e1902118, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31328882

RESUMEN

As a solid precursor to O2 and hydrogen peroxide (H2 O2 ), calcium peroxide (CaO2 ) has found widespread use in applications related to disinfection and contaminant degradation. The lack of uniform nanoparticles, however, greatly limits the potential use of this material in other applications related to medicine. Here, a new route to the facile synthesis of CaO2 nanocrystals and their spherical aggregates with uniform, controllable sizes is reported. The synthesis involves the reaction between CaCl2 and H2 O2 to generate CaO2 primary nanocrystals of 2-15 nm in size in ethanol, followed by their aggregation into uniform, spherical particles with the aid of poly(vinyl pyrrolidone) (PVP). The average diameter of the spherical aggregates can be easily tuned in the range of 15-100 nm by varying the concentrations of CaCl2 and/or PVP. For the spherical aggregates with a smaller size, they release H2 O2 and O2 more quickly when exposed to water, resulting in superior antimicrobial activity. This study not only demonstrates a new route to the synthesis of uniform CaO2 nanocrystals and their spherical aggregates but also offers a promising bacteriostatic agent with biodegradability.


Asunto(s)
Nanopartículas del Metal/química , Nanopartículas/química , Peróxidos/química , Antibacterianos/química , Cloruro de Calcio/química , Hidrógeno/química , Peróxido de Hidrógeno/química , Oxígeno/química , Polivinilos/química , Pirrolidinas/química
5.
Ann Plast Surg ; 80(3): 242-244, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28930783

RESUMEN

INTRODUCTION: Several factors may influence aesthetic outcomes of ptosis surgery, especially in patients with asymmetrical ptosis. We retrospectively assessed the effect of Hering's law on surgical outcomes of patients with asymmetrical ptosis. METHODS: Patients with mild to moderate asymmetrical ptosis (N = 300) who underwent advancement or plication of upper eyelid aponeurosis between January 2014 and July 2016 were enrolled. Fifty patients (group A) underwent surgery without taking into consideration the impact of Hering's law. Of these, 35 patients with unilateral ptosis (subgroup A1) underwent standard surgery on the contralateral side, whereas 15 patients with bilateral ptosis (subgroup A2) were first operated on the milder side followed by the more severely affected side.In 250 patients (group B), surgery was performed taking cognizance of the implications of Hering's law. These included 100 patients with unilateral ptosis (B1) and 150 with bilateral ptosis (B2). Difference in bilateral palpebral fissure symmetry by less than 0.5 mm was considered as satisfactory outcome. RESULTS: Duration of postoperative follow-up ranged from 3 to 24 months. Satisfactory outcomes were achieved over 60% of patients in group A (A1, 60.6%; A2, 66.67%) and in 96% of patients in group B (B1, 95%; B2, 96.67%). Patients with unsatisfactory outcomes underwent repair according to Hering's law after 3 months and obtained good results. CONCLUSIONS: Application of Hering's law may improve outcomes of corrective surgery in patients with asymmetric ptosis.


Asunto(s)
Blefaroplastia/métodos , Blefaroptosis/cirugía , Adulto , Estética , Femenino , Humanos , Masculino , Estudios Retrospectivos , Resultado del Tratamiento
6.
Nanomedicine ; 13(5): 1607-1616, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28285157

RESUMEN

Thermosensitive yolk-shell nanoparticles were developed as remote-controlled targeting drug delivery platform for multimodal imaging and combined therapy of cancer. The nanoparticles were fabricated using magnetic Fe3O4 nanoparticles as photothermal cores, thermo-responsive poly(N-isopropylacrylamide)-co-1-Vinyl-2-pyrrolidone p(NIPAM-co-NVP) as shells (Fe3O4-PNIPAM), with a hollow space between the two layers for loading of chemotherapeutic drug. The magnetic iron oxide nanoparticle cores could absorb and transform light to heat efficiently upon the irradiation of near infrared (NIR) laser, resulting in the shrink of the PNIPAM shell and the release of chemo-drugs. In vivo fluorescence/photoacoustic images demonstrated that Fe3O4-PNIPAM nanoparticles could accumulate in the tumor after intravenous injection. Upon the irradiation of the NIR laser, DOX-Fe3O4-PNIPAM nanoparticles exhibited outstanding synergistic effect. The tumor inhibition rate increased from 40.3% (DOX-Fe3O4-PNIPAM alone) and 65.2% (Fe3O4-PNIPAM +NIR) to 91.5%. The results demonstrated that the NIR-responsive nanocarrier offers a novel strategy for cancer theranostics and combined therapy of cancer.


Asunto(s)
Rayos Infrarrojos , Imagen Multimodal , Nanopartículas , Animales , Neoplasias de la Mama , Sistemas de Liberación de Medicamentos , Humanos , Ratones , Neoplasias , Células Tumorales Cultivadas
7.
Front Surg ; 11: 1335796, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38486795

RESUMEN

Objectives: To evaluate the comparation of myocutaneous flap vs. skin flap in V-Y medial epicanthal fold reconstruction. Methods: The study, conducted from April 2017 to June 2022, involved two groups: group A, comprising 21 patients who underwent medial epicanthal fold restoration surgery using the V-Y advancement method with a skin flap, and group B, comprising 83 patients who underwent the same procedure, while with a myocutaneous flap for orbicularis oculi ring reconstruction. Intercanthal distances were measured preoperatively, recorded during preoperative and postoperative reviews, and assessed through a 4-point Likert satisfaction questionnaire. Results: A total of 104 patients were followed up for 6 months postoperatively. In group A, preoperative intercanthal distances ranged from 28.7 mm to 38.2 mm, increasing to 30.2 mm-40.6 mm postoperatively, with a mean increase of 3.0 mm (P < 0.05). In group B, preoperative distances ranged from 28.8 mm to 38.0 mm, increasing to 32.2 mm-41.5 mm postoperatively, with a mean increase of 3.9 mm (P < 0.05). Group B exhibited a higher overall satisfaction rate compared to group A. Conclusion: The myocutaneous flap V-Y procedure, employing the principle of orbicularis oculi ring reconstruction, achieves more stable postoperative results than the flap-only V-Y procedure. Consequently, it can be regarded as the preferred surgical technique.

8.
ACS Nano ; 18(3): 2261-2278, 2024 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-38207332

RESUMEN

Sepsis, which is the most severe clinical manifestation of acute infection and has a mortality rate higher than that of cancer, represents a significant global public health burden. Persistent methicillin-resistant Staphylococcus aureus (MRSA) infection and further host immune paralysis are the leading causes of sepsis-associated death, but limited clinical interventions that target sepsis have failed to effectively restore immune homeostasis to enable complete eradication of MRSA. To restimulate anti-MRSA innate immunity, we developed CRV peptide-modified lipid nanoparticles (CRV/LNP-RNAs) for transient in situ programming of macrophages (MΦs). The CRV/LNP-RNAs enabled the delivery of MRSA-targeted chimeric antigen receptor (CAR) mRNA (SasA-CAR mRNA) and CASP11 (a key MRSA intracellular evasion target) siRNA to MΦs in situ, yielding CAR-MΦs with boosted bactericidal potency. Specifically, our results demonstrated that the engineered MΦs could efficiently phagocytose and digest MRSA intracellularly, preventing immune evasion by the "superbug" MRSA. Our findings highlight the potential of nanoparticle-enabled in vivo generation of CAR-MΦs as a therapeutic platform for multidrug-resistant (MDR) bacterial infections and should be confirmed in clinical trials.


Asunto(s)
Liposomas , Staphylococcus aureus Resistente a Meticilina , Nanopartículas , Receptores Quiméricos de Antígenos , Sepsis , Infecciones Estafilocócicas , Animales , Ratones , Receptores Quiméricos de Antígenos/uso terapéutico , Infecciones Estafilocócicas/tratamiento farmacológico , ARN Mensajero , Antibacterianos/farmacología , Macrófagos , Sepsis/tratamiento farmacológico , Lípidos/farmacología
9.
Micromachines (Basel) ; 14(2)2023 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-36838112

RESUMEN

An efficient multi-objective optimization method of temperature and stress for a microsystem based on particle swarm optimization (PSO) was established, which is used to map the relationship between through-silicon via (TSV) structural design parameters and performance objectives in the microsystem, and complete optimization temperature, stress and thermal expansion deformation efficiently. The relationship between the design and performance parameters is obtained by a finite element method (FEM) simulation model. The neural network is built and trained in order to understand the mapping relationship. Then, the design parameters are iteratively optimized using the PSO algorithm, and the FEM results are used to verify the efficiency and reliability of the optimization methods. When the optimization target of peak temperature, bump temperature, TSV temperature, maximum stress and maximum thermal deformation are set as 100 °C, 55 °C, 35 °C, 180 Mpa and 12 µm, the optimization results are as follows: the peak temperature is 97.90 °C, the bump temperature is 56.01 °C, the TSV temperature is 31.52 °C, the maximum stress is 247.4 Mpa and the maximum expansion deformation is 11.14 µm. The corresponding TSV structure design parameters are as follows: the radius of TSV is 10.28 µm, the pitch is 65 µm and the thickness of SiO2 is 0.83 µm. The error between the optimization result and the target temperature is 2.1%, 1.8%, 9.9%, 37.4% and 7.2% respectively. The PSO method has been verified by regression analysis, and the difference between the temperature and deformation optimization results of the FEM method is not more than 3%. The stress error has been analyzed, and the reliability of the developed method has been verified. While ensuring the accuracy of the results, the proposed optimization method reduces the time consumption of a single simulation from 2 h to 70 s, saves a lot of time and human resources, greatly improves the efficiency of the optimization design of microsystems, and has great significance for the development of microsystems.

10.
Cyborg Bionic Syst ; 4: 0058, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37829507

RESUMEN

Everyday unnatural events such as trauma, accidents, military conflict, disasters, and even medical malpractice create open wounds and massive blood loss, which can be life-threatening. Fractures and large bone defects are among the most common types of injuries. Traditional treatment methods usually involve rapid hemostasis and wound closure, which are convenient and fast but may result in various complications such as nerve injury, deep infection, vascular injury, and deep hematomas. To address these complications, various studies have been conducted on new materials that can be degraded in the body and reduce inflammation and abscesses in the surgical area. This review presents the latest research progress in biomaterials for bone hemostasis and repair. The mechanisms of bone hemostasis and bone healing are first introduced and then principles for rational design of biomaterials are summarized. After providing representative examples of hemostatic biomaterials for bone repair, future challenges and opportunities in the field are proposed.

11.
Nat Commun ; 14(1): 817, 2023 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-36781864

RESUMEN

Massive intra-articular infiltration of proinflammatory macrophages is a prominent feature of rheumatoid arthritis (RA) lesions, which are thought to underlie articular immune dysfunction, severe synovitis and ultimately joint erosion. Here we report an efferocytosis-informed nanoimitator (EINI) for in situ targeted reprogramming of synovial inflammatory macrophages (SIMs) that thwarts their autoimmune attack and reestablishes articular immune homeostasis, which mitigates RA. The EINI consists of a drug-based core with an oxidative stress-responsive phosphatidylserine (PtdSer) corona and a shell composed of a P-selectin-blocking motif, low molecular weight heparin (LMWH). When systemically administered, the LMWH on the EINI first binds to P-selectin overexpressed on the endothelium in subsynovial capillaries, which functions as an antagonist, disrupting neutrophil synovial trafficking. Due to the strong dysregulation of the synovial microvasculature, the EINI is subsequently enriched in the joint synovium where the shell is disassembled upon the reactive oxygen species stimulation, and PtdSer corona is then exposed. In an efferocytosis-like manner, the PtdSer-coroneted core is in turn phagocytosed by SIMs, which synergistically terminate SIM-initiated pathological cascades and serially reestablish intra-articular immune homeostasis, conferring a chondroprotective effect. These findings demonstrate that SIMs can be precisely remodeled via the efferocytosis-mimetic strategy, which holds potential for RA treatment.


Asunto(s)
Artritis Reumatoide , Selectina-P , Ratones , Animales , Selectina-P/metabolismo , Heparina de Bajo-Peso-Molecular , Articulaciones/metabolismo , Membrana Sinovial/metabolismo
12.
Sci Adv ; 9(22): eadg3365, 2023 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-37256944

RESUMEN

Tracking and eradicating Staphylococcus aureus in the periprosthetic microenvironment are critical for preventing periprosthetic joint infection (PJI), yet effective strategies remain elusive. Here, we report an implant nanoparticle coating that locoregionally yields bactericidal super chimeric antigen receptor macrophages (CAR-MΦs) to prevent PJI. We demonstrate that the plasmid-laden nanoparticle from the coating can introduce S. aureus-targeted CAR genes and caspase-11 short hairpin RNA (CASP11 shRNA) into macrophage nuclei to generate super CAR-MΦs in mouse models. CASP11 shRNA allowed mitochondria to be recruited around phagosomes containing phagocytosed bacteria to deliver mitochondria-generated bactericidal reactive oxygen species. These super CAR-MΦs targeted and eradicated S. aureus and conferred robust bactericidal immunologic activity at the bone-implant interface. Furthermore, the coating biodegradability precisely matched the bone regeneration process, achieving satisfactory osteogenesis. Overall, our work establishes a locoregional treatment strategy for priming macrophage-specific bactericidal immunity with broad application in patients suffering from multidrug-resistant bacterial infection.


Asunto(s)
Receptores Quiméricos de Antígenos , Staphylococcus aureus , Animales , Ratones , Oseointegración , Antibacterianos/farmacología , Macrófagos/microbiología
13.
Medicine (Baltimore) ; 101(35): e30409, 2022 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-36107593

RESUMEN

Double-eyelid surgery is a very common practice in East Asian patients. The differential distribution of pretarsal tissue layers is considered to be the anatomical mechanism of natural Asiatic single eyelid, it is possible to form double-eyelid crease by re-positioning the pretarsal structure layers. The author presents a new double-eyelid surgery based on re-positioning of the pretarsal structure layers without tissue removal. Over a 6-year period, 1440 patients underwent new double-eyelid surgeries. With the pretarsal orbicularis oculi muscle incised, the pre-pretarsal levator aponeurosis fascia fibroadipose was first dissected to form a fibroadipose flap, and then repositioned with the eyelid lower lip orbicularis oculi muscle flap. The new composite structure was anchored at 3 points on the pretarsal levator aponeurosis fascia; the skin was sutured to form a smooth crease. Post-operative outcome and follow-up data were analyzed. Patients were followed up for an average of 2 years. esthetic outcomes were satisfactory for 97.91% of patients, who enjoyed new double upper eyelids with smooth creases and invisible incision lines. Outcomes were unsatisfactory for 2.08% of patients (double-eyelid regression, 0.76%; asymmetric creases, 1.32%). All patients who were not satisfied with their esthetic outcomes underwent second correction surgery. This new Pan-flap technique focuses on the correct dissection and repositioning of differentially thickened pre-pretarsal levator aponeurosis fascia fibroadipose tissue in East Asian patients. This new technique can generate broader and tighter attachment between pretarsal orbicularis oculi muscle and levator aponeurosis fascia, and form smooth double-eyelid crease without pretarsal soft tissue removal.


Asunto(s)
Blefaroplastia , Aponeurosis , Blefaroplastia/métodos , Estética , Párpados/cirugía , Músculos Faciales , Humanos
14.
Front Microbiol ; 13: 989272, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36160214

RESUMEN

Arsenic contamination causes numerous health problems for humans and wildlife via bioaccumulation in the food chain. Phytoremediation of arsenic-contaminated soils with the model arsenic hyperaccumulator Pteris vittata provides a promising way to reduce the risk, in which the growth and arsenic absorption ability of plants and the biotransformation of soil arsenic may be greatly affected by rhizosphere microorganisms. However, the microbial community composition in the rhizosphere of P. vittata and its functional role in arsenic phytoremediation are still poorly understood. To bridge this knowledge gap, we carried out a field investigation and pot experiment to explore the composition and functional implications of microbial communities in the rhizosphere of four P. vittata populations with a natural arsenic contamination gradient. Arsenic pollution significantly reduced bacterial and fungal diversity in the rhizosphere of P. vittata (p < 0.05) and played an important role in shaping the microbial community structure. The suitability of soil microbes for the growth of P. vittata gradually decreased following increased soil arsenic levels, as indicated by the increased abundance of pathogenic fungi and parasitic bacteria and the decrease in symbiotic fungi. The analysis of arsenic-related functional gene abundance with AsChip revealed the gradual enrichment of the microbial genes involved in As(III) oxidation, As(V) reduction, and arsenic methylation and demethylation in the rhizosphere of P. vittata following increased arsenic levels (p < 0.05). The regulation of indigenous soil microbes through the field application of fungicide, but not bactericide, significantly reduced the remediation efficiency of P. vittata grown under an arsenic contamination gradient, indicating the important role of indigenous fungal groups in the remediation of arsenic-contaminated soil. This study has important implications for the functional role and application prospects of soil microorganisms in the phytoremediation of arsenic-polluted soil.

15.
Nanoscale ; 14(41): 15543, 2022 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-36239284

RESUMEN

Correction for 'Eliciting an immune hot tumor niche with biomimetic drug-based multi-functional nanohybrids augments immune checkpoint blockade-based breast cancer therapy' by Wei Du et al., Nanoscale, 2020, 12, 3317-3329, https://doi.org/10.1039/C9NR09835F.

16.
Sci Transl Med ; 14(656): eabn1128, 2022 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-35921473

RESUMEN

Glioblastoma multiforme (GBM) remains incurable despite aggressive implementation of multimodal treatments after surgical debulking. Almost all patients with GBM relapse within a narrow margin around the initial resected lesion due to postsurgery residual glioma stem cells (GSCs). Tracking and eradicating postsurgery residual GSCs is critical for preventing postoperative relapse of this devastating disease, yet effective strategies remain elusive. Here, we report a cavity-injectable nanoporter-hydrogel superstructure that creates GSC-specific chimeric antigen receptor (CAR) macrophages/microglia (MΦs) surrounding the cavity to prevent GBM relapse. Specifically, we demonstrate that the CAR gene-laden nanoporter in the hydrogel can introduce GSC-targeted CAR genes into MΦ nuclei after intracavity delivery to generate CAR-MΦs in mouse models of GBM. These CAR-MΦs were able to seek and engulf GSCs and clear residual GSCs by stimulating an adaptive antitumor immune response in the tumor microenvironment and prevented postoperative glioma relapse by inducing long-term antitumor immunity in mice. In an orthotopic patient-derived glioblastoma humanized mouse model, the combined treatment with nanoporter-hydrogel superstructure and CD47 antibody increased the frequency of positive immune responding cells and suppressed the negative immune regulating cells, conferring a robust tumoricidal immunity surrounding the postsurgical cavity and inhibiting postoperative glioblastoma relapse. Therefore, our work establishes a locoregional treatment strategy for priming cancer stem cell-specific tumoricidal immunity with broad application in patients suffering from recurrent malignancies.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Glioma , Receptores Quiméricos de Antígenos , Animales , Neoplasias Encefálicas/genética , Línea Celular Tumoral , Glioblastoma/genética , Glioma/patología , Glioma/terapia , Hidrogeles , Macrófagos/patología , Ratones , Recurrencia Local de Neoplasia/patología , Células Madre Neoplásicas/patología , Microambiente Tumoral , Ensayos Antitumor por Modelo de Xenoinjerto
17.
Adv Mater ; 34(14): e2107506, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35146813

RESUMEN

Idiopathic pulmonary fibrosis (IPF), a lethal respiratory disease with few treatment options, occurs due to repetitive microinjuries to alveolar epithelial cells (AECs) and progresses with an overwhelming deposition of extracellular matrix (ECM), ultimately resulting in fibrotic scars and destroyed the alveolar architecture. Here, an inhaled ribosomal protein-based mRNA nanoformulation is reported for clearing the intrapulmonary ECM and re-epithelializing the disrupted alveolar epithelium, thereby reversing established fibrotic foci in IPF. The nanoformulation is sequentially assembled by a ribosomal protein-condensed mRNA core, a bifunctional peptide-modified corona and keratinocyte growth factor (KGF) with a PEGylated shielding shell. When inhaled via a nebulizer, the nanoformulations carried by microdrops are deposited in the alveoli, and penetrate into fibrotic foci, where the outer KGFs are detached after matrix metalloproteinase 2 (MMP2) triggering. The RGD motif-grafted cores then expose and specifically target the integrin-elevated cells for the intracellular delivery of mRNA. Notably, repeated inhalation of the nanoformulations accelerates the clearance of locoregional collagen by boosting the intralesional expression of MMP13 and alveolar re-epithelialization mediated by KGFs, which synergistically ameliorates the lung function of a bleomycin-induced murine model. Therefore, this work provides an alternative mRNA-inhalation delivery strategy, which shows great potential for the treatment of IPF.


Asunto(s)
Bleomicina , Fibrosis Pulmonar Idiopática , Animales , Bleomicina/farmacología , Modelos Animales de Enfermedad , Fibrosis Pulmonar Idiopática/inducido químicamente , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/genética , Metaloproteinasa 2 de la Matriz/genética , Ratones , ARN Mensajero , Proteínas Ribosómicas
18.
Polymers (Basel) ; 13(15)2021 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-34372156

RESUMEN

A novel intumescent flame retardant (IFR) agent designated as Dohor-6000A has been used to prepare halogen-free flame retardant polypropylene (PP) fibers via melting spinning. Before being blended with PP resin, a surface modification of Dohor-6000A was carried out to improve its compatibility with the PP matrix. The rheological behavior of flame retardant Dohor-6000A/PP resin, the structure, morphology, mechanical properties, flammability of the Dohor-6000A/PP fibers were studied in detail, as well as the action mode of flame retardant. X-ray diffraction (XRD) showed that the addition of Dohor-6000A did not damage the crystal as well as the orientation structure of PP matrix, which was helpful to the maintenance of mechanical properties. The presence of the IFR significantly improved the flame retardant performance and thermal stability of PP fibers. When the content of Dohor-6000A reached 25%, the fibers displayed a limiting oxygen index (LOI) value of 29.1% and good melt-drop resistance. Moreover, the peak heat release rate (PHRR) and total heat release (THR) from microscale combustion colorimetry (MCC) tests were decreased by 26.0% and 16.0% in comparison with the same conditions for pure PP fibers. In the condensed phase, the IFR promoted a carbonization process and promoted the formation of a glassy or stable foam protective layer on the surface of the polymer matrix. In addition, the IFR decomposed endothermically to release of non-combustible gases such as NH3 and CO2 which dilutes the combustible gases in the combustion zone.

19.
Nat Nanotechnol ; 16(5): 538-548, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33526838

RESUMEN

Immunotherapies have revolutionized intervention strategies for many primary cancers, but have not improved the outcomes of glioblastoma multiforme (GBM), which remains one of the most lethal malignant cerebral tumours. Here we present an injectable hydrogel system that stimulates tumoricidal immunity after GBM surgical resection, which mitigates its relapse. The hydrogel comprises a tumour-homing immune nanoregulator, which induces immunogenic cell death and suppression of indoleamine 2,3-dioxygenase-1, and chemotactic CXC chemokine ligand 10, for a sustained T-cell infiltration. When delivered in the resected tumour cavity, the hydrogel system mimics a 'hot' tumour-immunity niche for attacking residual tumour cells and significantly suppresses postoperative GBM recurrence. Our work provides an alternative strategy for conferring effective tumoricidal immunity in GBM patients, which may have a broad impact in the immunotherapy of 'cold' tumours after surgical intervention.


Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Antineoplásicos Inmunológicos/uso terapéutico , Quimiocina CXCL10/uso terapéutico , Glioblastoma/terapia , Hidrogeles/uso terapéutico , Recurrencia Local de Neoplasia/prevención & control , Adyuvantes Inmunológicos/administración & dosificación , Animales , Antineoplásicos Inmunológicos/administración & dosificación , Células Cultivadas , Quimiocina CXCL10/administración & dosificación , Femenino , Glioblastoma/inmunología , Glioblastoma/cirugía , Humanos , Hidrogeles/administración & dosificación , Muerte Celular Inmunogénica/efectos de los fármacos , Inmunoterapia , Ratones Endogámicos C57BL , Nanomedicina , Recurrencia Local de Neoplasia/inmunología , Ratas Wistar
20.
Biol Rev Camb Philos Soc ; 96(6): 2771-2793, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34288351

RESUMEN

Phosphate-solubilizing microbes (PSMs) drive the biogeochemical cycling of phosphorus (P) and hold promise for sustainable agriculture. However, their global distribution, overall diversity and application potential remain unknown. Here, we present the first synthesis of their biogeography, diversity and utility, employing data from 399 papers published between 1981 and 2017, the results of a nationwide field survey in China consisting of 367 soil samples, and a genetic analysis of 12986 genome-sequenced prokaryotic strains. We show that at continental to global scales, the population density of PSMs in environmental samples is correlated with total P rather than pH. Remarkably, positive relationships exist between the population density of soil PSMs and available P, nitrate-nitrogen and dissolved organic carbon in soil, reflecting functional couplings between PSMs and microbes driving biogeochemical cycles of nitrogen and carbon. More than 2704 strains affiliated with at least nine archaeal, 88 fungal and 336 bacterial species were reported as PSMs. Only 2.59% of these strains have been tested for their efficiencies in improving crop growth or yield under field conditions, providing evidence that PSMs are more likely to exert positive effects on wheat growing in alkaline P-deficient soils. Our systematic genetic analysis reveals five promising PSM genera deserving much more attention.


Asunto(s)
Fosfatos , Microbiología del Suelo , Agricultura/métodos , Fósforo , Suelo
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